HERNANDEZ v. SECRETARY OF HEALTH AND HUMAN SERVICES

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 17-0143V

Filed: December 15, 2023

Special Master Horner

VALERIA HERNANDEZ, as the legal

representative of her minor daughter,

S.H.

Petitioner,

v.

SECRETARY OF HEALTH AND

HUMAN SERVICES,

Respondent.

Curtis R. Webb, Monmouth, OR, for petitioner.

Alexa Roggenkamp, U.S. Department of Justice, Washington, DC, for respondent.

DECISION1

On January 30, 2017, petitioner filed a petition on behalf of her minor daughter

(“S.H.”) under the National Childhood Vaccine Injury Act (“Vaccine Act”), 42 U.S.C. §

300aa-10, et seq. (2018).2 (ECF No. 1.) Petitioner alleged that S.H. suffered seizures

leading to epilepsy caused by her May 22, 2015 Pediarix (consisting of diphtheria-

tetanus-accellular pertussis (“DTaP”); hepatitis B; and polio vaccines), haemophilus

influenzae B (“HIB”), pneumococcal conjugate (“Prevnar 13”), and rotavirus

vaccinations. (Id.) For the reasons discussed below, I conclude that petitioner is not

entitled to compensation.

1 Because this document contains a reasoned explanation for the action taken in this case, it must be

made publicly accessible and will be posted on the United States Court of Federal Claims' website, and/or

at https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government

Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic

Government Services). This means the document will be available to anyone with access to the

internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact

medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy.

If, upon review, I agree that the identified material fits within this definition, I will redact such material from

public access.

2 All references to “§ 300aa” below refer to the relevant section of the Vaccine Act at 42 U.S.C. § 300aa-

10-34.

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I. Applicable Statutory Scheme

Under the National Vaccine Injury Compensation Program, compensation

awards are made to individuals who have suffered injuries after receiving vaccines. In

general, to gain an award, a petitioner must make a number of factual demonstrations,

including showing that an individual received a vaccination covered by the statute;

received it in the United States; suffered a serious, long-standing injury; and has

received no previous award or settlement on account of the injury. Finally – and the key

question in most cases under the Program – the petitioner must also establish a causal

link between the vaccination and the injury. In some cases, the petitioner may simply

demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be

shown that the vaccine recipient suffered an injury of the type enumerated in the

“Vaccine Injury Table,” corresponding to the vaccination in question, within an

applicable time period also specified in the Table. If so, causation is presumed and the

petitioner is automatically entitled to compensation, unless it is affirmatively shown that

the injury was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A); §

300 aa-11(c)(1)(C)(i); § 300aa-14(a); § 300aa-13(a)(1)(B).

In many cases, however, the vaccine recipient may have suffered an injury not of

the type covered in the Vaccine Injury Table. In these cases, the presumptions

available under the Vaccine Injury Table are inoperative. Instead, the petitioner bears

the burden of showing by preponderant evidence that the vaccine recipient’s injury was

actually caused by the alleged vaccination, often referred to as “causation-in-fact”. §

300aa-13(a)(1)(B); § 300aa-11(c)(1)(C)(ii); see also Althen v. Sec’y of Health & Human

Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005); Hines v. Sec’y of Health & Human Servs.,

940 F.2d 1518, 1525 (Fed. Cir. 1991). In this case, petitioner alleges S.H. suffered

seizures and epilepsy, which are not Table injuries. Nor does petitioner otherwise

allege that these injuries constitute manifestations of any Table injury. Accordingly,

petitioner must satisfy the burden of proof for “causation-in-fact.”

Under the causation-in-fact standard, the petitioner must show that it is “more

probable than not” that the alleged vaccination was the cause of the alleged injury.

Althen, 418 F.3d at 1279. The petitioner need not show that the vaccination was the

sole cause of the injury, but must establish that the vaccination was at least a

“substantial factor” and “but for” cause of the condition. Shyface v. Sec’y of Health &

Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999). A petitioner may not receive a

Vaccine Program award based solely on his or her assertions; rather, the petition must

be supported by either medical records or by the opinion of a competent physician. §

300aa-13(a)(1). The petitioner must supply “proof of a logical sequence of cause and

effect showing that the vaccination was the reason for the injury;” and this proof must be

supported by “reputable medical or scientific explanation, i.e., evidence in the form of

scientific studies or expert medical testimony.” Althen, 418 F.3d at 1278; Grant v. Sec’y

of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992).

In what has become the predominant framing of this burden of proof, the Althen

court described the causation-in-fact standard, as follows:

2

Concisely stated, Althen’s burden is to show by preponderant evidence that

the vaccination brought about her injury by providing: (1) a medical theory

causally connecting the vaccination and the injury; (2) a logical sequence

of cause and effect showing that the vaccination was the reason for the

injury; and (3) a showing of proximate temporal relationship between

vaccination and injury. If Althen satisfies this burden, she is “entitled to

recover unless the [government] shows, also by a preponderance of the

evidence, that the injury was in fact caused by factors unrelated to the

vaccine.”

Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner

need not necessarily supply evidence from medical literature supporting petitioner’s

causation contention, so long as the petitioner supplies the medical opinion of an

expert. Id. at 1279-80. The court also indicated that, in finding causation, a Program

fact-finder may rely upon “circumstantial evidence,” which the court found to be

consistent with the “system created by Congress, in which close calls regarding

causation are resolved in favor of injured claimants.” Id. at 1280.

Generally, respondent bears the burden of demonstrating the presence of any

alternative cause by preponderant evidence only if petitioner satisfies her prima facie

burden. § 300aa-13(a)(1)(B); Walther v. Sec’y of Health & Human Servs., 485 F.3d

1146, 1150 (Fed. Cir. 2007). Respondent may also present evidence relating to an

alternative cause to demonstrate the inadequacy of petitioner’s evidence supporting her

case in chief, but petitioner does not bear the burden of eliminating alternative causes

where the other evidence on causation is sufficient to establish a prima facie case under

Althen. de Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352-53 (Fed.

Cir. 2008); Walther, 485 F.3d at 1150.

II. Procedural History

Petitioner filed her petition for compensation on January 30, 2017. (ECF No. 1.)

Petitioner also filed an affidavit and several medical records. (Exs. 1-6.) The following

day, this case was assigned to Special Master Millman, who subsequently ordered

petitioner to file an expert report supporting her claim. (ECF No. 4.) Special Master

Millman issued an order setting out a series of issues, including whether petitioner had

satisfied the six-month severity requirement and whether S.H.’s parents may have

misinterpreted her spells based on their identification of events that were not recorded

as seizures during the EEGs. (ECF No. 7.) She ordered petitioner to file an expert

report. (ECF No. 10.)

Petitioner filed an expert report from Dr. Marcel Kinsbourne with accompanying

literature in October of 2017. (ECF No. 13-15; Exs. 7-23.) In January of 2018,

respondent filed his Rule 4 report, recommending against compensation, along with an

expert report by Dr. Gregory Holmes and supporting medical literature. (ECF Nos. 18-

21; Exs. A-B.) Petitioner filed a supplemental expert report and supporting literature

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from Dr. Kinsbourne the following May. (ECF No. 25, 27; Exs. 24-26.) Respondent

filed a supplemental expert report from Dr. Holmes in July of 2018. (ECF No. 29; Ex.

C.)

Thereafter, Special Master Millman issued an order queuing the case for an

entitlement hearing following her retirement. (ECF No. 30.) This case was reassigned

to my docket in June of 2019. (ECF Nos. 32-33.) I ordered petitioner to file updated

medical records, which were filed in March of 2020. (ECF Nos. 34, 36; Ex. 27.) I held a

follow up status conference with the parties in April of 2020. (ECF No. 37.) I explained

that, based on my review of the updated medical records, it appeared that the question

of the statutory severity requirement would likely turn on S.H.’s treatment with

phenobarbital. (Id. at 1.) I also encouraged the parties to review a separate decision I

issued in Kottenstette v. Secretary of Health & Human Services, No. 15-1016V, 2020

WL 4197301 (Fed. Cl. Spec. Mstr. June 2, 2020).3 (ECF No. 38.)

An entitlement hearing was set in this case to be held in August of 2022. (ECF

No. 44.) In the interim, petitioner filed a further supplemental report by Dr. Kinsbourne

and respondent filed a responsive report by Dr. Holmes along with an additional report

by Dr. Herman Staats. (ECF Nos. 46, 49, 52-55, 57-61; Exs. 28-44, D-E.) Petitioner

filed her final expert report from Dr. Kinsbourne on February 28, 2022, and respondent

filed his final reports on May 6, 2022. (ECF Nos. 65, 71; Exs. 45-53; Exs. G-H.)

An entitlement hearing was held on August 16, 2022. (See Transcript of

Proceedings (“Tr.") at ECF No. 86.) Petitioner, Dr. Kinsbourne, Dr. Holmes, and Dr.

Staats testified. This case is now ripe for a ruling on entitlement. (See Tr. 161 (counsel

agreeing record is closed).)

III. Factual History

a. As Reflected in the Medical Records

S.H. was born on January 19, 2015 by cesarean section. (Ex. 2, p. 4.) She had

no significant health issues at the time of her birth beyond a minor heart murmur and a

ventricular septal defect (“VSD”). (Id. at 4-8.) S.H. was discharged home with her

parents on January 23, 2015. (Id.) S.H. continued to receive regular wellness-checks

after her discharge with no major abnormalities. (See Ex. 3, pp. 2-12, 13-16, 43-47.)

S.H. also received a pediatric cardiology consult for her VSD from Dr. Joseph Mares.

(Ex. 3, pp. 30-37.) During this visit, S.H.’s exam was normal, and Dr. Mares believed

that her VSD would ultimately resolve on its own. (Id.) Petitioner received an EKG from

Dr. Mares on February 24, 2015, which showed that her VSD was indeed getting

smaller. (Id. at 64.)

S.H. received her first doses of the subject vaccinations, without issue, during her

2-month well child visit on March 20, 2015. (Ex. 3, pp. 88-94.) S.H. then received the

3 This decision was subsequently vacated by the Federal Circuit for unrelated reasons. See Kottenstette

v. Sec’y of Health & Human Servs., 861 Fed. App’x 433 (Fed. Cir. 2021).

4

second doses of the subject vaccinations at her 4-month well child visit on May 22,

2015. (Id. at 110-16.) S.H. was brought to the emergency room several hours after

receiving her May 22 vaccinations. (Ex. 4, pp. 5-59.) Petitioner reported that, after her

vaccinations, S.H. experienced a “[generalized tonic-clonic] seizure with eyes rolling

back, lasting 2-3 min, in afternoon while in car seat.” (Id. at 6.) S.H. was taken to the

emergency department at PIH Health Hospital (“PIH”) where she had a second seizure

that lasted about one minute. (Id.) She underwent a CT scan and laboratory testing

before being transferred to Kaiser Permanente Hospital (“Kaiser”). (Id.) The treating

physician at Kaiser, Christopher Chinnici, M.D., noted a normal exam, unremarkable

laboratory testing, and no abnormalities on S.H.’s CT scan and believed that S.H.’s

seizures were provoked by her vaccinations. (Id. at 9-10, 54.) S.H. also received a

neurology consultation from Shelley Bose, M.D., while she was at Kaiser. (Id. at 10-12.)

Dr. Bose noted that S.H. had no concerning personal or family history that would

explain her seizures, and she spoke to petitioner and her husband about the risks of

vaccine provoked seizures. (Id. at 11.) S.H. did not experience any further seizures at

this visit and was discharged on May 23, 2015, with the recommendation that petitioner

continue to monitor S.H. for any further signs of seizures. (Id. at 10.)

Petitioner returned with S.H. to the emergency department at PIH on May 26,

2015. (Ex. 6, p. 52.) Petitioner reported to staff that S.H. had experienced another two

seizures that morning. (Id.) Petitioner described the seizures as occurring when S.H.

would wake up and involving “right eye deviation, lip smacking, arms shaking,” and

lasting for one to two minutes. (Id.) S.H. did not exhibit a fever or lethargy on this visit,

and her physical exam was normal. (Id.) Petitioner’s CSF panel did reveal “some

atypical cells concerning for possible leukemia,” but the attending pathologist believed

the results were due to a traumatic spinal tap. (Id. at 53.) During her observation

period, S.H. did not exhibit any signs of seizure, and an attending nurse wrote that she

was unable to identify any seizure activity during one period where S.H.’s parents

believed that she was experiencing another seizure. (Ex. 4, p. 85.) S.H. was

subsequently transferred to Kaiser for further observation. (Id. at 70.)

On admission at Kaiser, petitioner attributed S.H.’s seizures to her vaccinations,

and explained that she believed S.H. had “been having subacute spells for a longer time

and more frequently as she describes her often waking with stiff extremities and lip

smacking, and possibly staring, but no obvious [generalized tonic-clonic] motions.” (Ex.

4, pp.74-75.) S.H’s exam was normal and no further seizures were reported. (Id. at

78.) S.H. also underwent a 24-hour EEG on May 27, 2015. (Id. at 81-82.) Although

petitioner believed that S.H. experienced multiple seizures during the monitoring phase

of her EEG, there were no signs of any seizure activity. (Id.) The treating physician at

Kaiser, Dr. Fuqua, noted that “the spells being described may or may not be seizures,

as mother does not report [S.H.] is sleepy or inactive (eg postictal) after.” (Id. at 79.)

S.H. was ultimately diagnosed with “absence epilepsy” and discharged home on May

27, 2015. (Id. at 78-79.)

The following day, S.H. was again brought to the emergency department at PIH

with complaints of a generalized tonic-clonic seizure. (Ex. 6, p. 109.) Petitioner

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explained that as S.H. woke up in the morning, her “eyes rolled up, her arms were tight

with increased tone in her arms and legs were trembling lasting from 1-2 minutes.” (Id.)

S.H. was observed and her neurologist, Dr. Bose, was contacted.4 (Id. at 110.) Dr.

Bose recommended starting S.H. on phenobarbital and possibly adding Keppra at a

later date. (Id.) S.H. was transferred to Kaiser for observation and did not exhibit any

further seizures after receiving her initial phenobarbital dose. (Ex. 4, pp. 158-61.) S.H.

was discharged on May 30, 2015, with an updated diagnosis of epilepsy and a

prescription for phenobarbital. (Id. at 148-58.)

S.H. was next brought to neurologist Mi-Kyung Lee, M.D., on June 4, 2015, for a

follow up on her seizures. (Ex. 5, p. 2.) Dr. Lee noted that the seizures were “initially

attributed to vaccines but persisted well after 72 hours,” and that S.H. had no problems

with her phenobarbital prescription beyond mild drowsiness. (Id.) S.H. underwent a

second 24-hour EEG on June 24, 2015, the results of which were normal. (Id. at 36-

37.) On June 26, 2015, petitioner called Dr. Bose’s office to report what she believed to

be another seizure where S.H. “shook her hands from side to side lasting 3 to 5

seconds when she was falling asleep and bottle was being removed.” (Id. at 23.) Dr.

Bose advised petitioner to continue monitoring the event and to film it if possible, but

“based on the description, [Dr. Bose was] not convinced it represents a seizure.” (Id. at

22.) Petitioner emailed Dr. Bose again on July 16, 2015, referencing a German case

study documenting an afebrile seizure in a vaccinee within 7 days after administration of

the Pediarix vaccine and asking if S.H.’s seizures could have been caused by her

vaccinations. (Id. at 42-43.) She further requested a referral for S.H. to see Dean

Sarco, M.D., for a second opinion. (Id.) Dr. Bose responded that a single case report is

insufficient to attribute causation to the vaccines; however, she referred S.H. to Dr.

Sarco as requested. (Id.)

On July 24, 2015, S.H. was seen by Jennifer Varghese, M.D., for head control

problems. (Ex. 5, p. 61.) Dr. Varghese reviewed videos that petitioner had taken of

S.H. and concluded that, despite there appearing to be some lack of head control, there

was no seizure activity and S.H. appeared to be developing normally. (Id. at 62.) Dr.

Varghese’s assessment was “PERSON W FEARED COMPLAINT,” and she declined to

make a diagnosis. (Id.)

S.H. saw Dr. Sarco on July 27, 2015, for a second opinion on her epilepsy. (Ex.

5, p. 69.) Dr. Sarco recorded a normal exam and noted that it was unclear if S.H.’s

seizures were caused by her vaccinations or were secondary to a mild epilepsy. (Id. at

71.) He suspected that S.H. “has a mildly increased risk for seizures inherently,” and

recommended continuing phenobarbital at least through her 12-month vaccinations.

(Id. at 71-72.) S.H. continued to take phenobarbital with no issues and Dr. Sarco began

discussing weaning her off the medication in October of 2015, however, ultimately

decided that S.H. should not be weaned until after her first year vaccinations. (Id. at

165, 172-74, 229.) Petitioner began weaning S.H. in the beginning of April 2016. (Id. at

306-08.) S.H. continued to receive her typical vaccinations on a more spread-out

schedule, and there have not been any additional seizures reported since May 28,

4 The record erroneously refers to Dr. Bose as “Dr. Boat.” (Ex. 6, pp. 109-10.)

6

2015. (Id. at 154-316.) In 2017, S.H. saw a speech therapist, however, had no speech

or developmental delays as a result of her seizures. (Ex. 27, pp. 399-406.)

b. As Reflected by Petitioner’s Testimony

Petitioner filed an affidavit and also testified during the hearing. (Ex. 1; Tr. 6-27.)

Petitioner recounted that S.H. received her 2-month vaccinations on March 20,

2015, after which, she “was very fussy . . . and had a slight temperature.” (Ex. 1, p. 2.)

She further states that on May 22, 2015, she took S.H. in for her 4-month check-up

where she received her 4-month vaccinations of Pediarix, HiB, Prevnar 13, and Rotarix.

(Id.; see also Tr. 8.) Petitioner stated that S.H. fell asleep on the way home following

her vaccinations, and that she was brought into the house in her car seat so as not to

wake her. (Ex. 1, p. 2-3; see also Tr. 8.) About 20 minutes after arriving home, S.H.

awoke and was “smacking her lips.” (Ex. 1, p. 3; see also Tr. 9.) After several seconds

of lip smacking, S.H.’s father called petitioner over to tell her something was wrong S.H.

(Ex. 1, p. 3.) Petitioner stated that it was at this point she “realized that [S.H.] was

having a seizure [and] immediately called 911.” (Id.; see also Tr. 9.) Petitioner

described S.H.’s seizure as involving her eyes rolling upward, arms and legs jerking,

and smacking her lips. (Ex. 1, p. 3.) S.H. was somewhat responsive after the seizure,

but she was not the happy and babbling baby that she usually was. (Tr. 9, 11.)

Petitioner described how S.H. cried “really loud” after she stopped seizing, and then

how she was “quieter than usual” but not quite drowsy. (Id. at 9-10.)

Petitioner stated that while S.H. was being prepared for discharge from PIH, she

had a second seizure with the same characteristics as the first. (Ex. 1, p. 3; see also Tr.

11-14.) The doctors ordered a CT scan to rule out any brain bleeding, and it came back

normal. (Ex. 1, p. 3; see also Tr. 11.) Petitioner affirmed that S.H. had a slight

temperature following her second seizure and was treated with Tylenol. (Ex. 1, p. 3.)

S.H. was then transferred to Kaiser where she was observed over 24 hours for any

additional seizure activity. (Id. at 4.) Petitioner affirmed that after meeting Dr. Bose,

S.H.’s pediatric neurologist, she was told that the DTaP components of the Pediarix

vaccine may have triggered S.H.’s seizures. (Id.; see also Tr. 14.) S.H. did not show

any signs of seizure during her observation period at Kaiser. (Ex. 1, p. 4.)

Petitioner reported that S.H. had a third seizure on May 26, 2015, with the same

characteristics as her first two seizures. (Ex. 1, p. 4; see also Tr. 15-18.) S.H. was

again taken to the PIH emergency room where she underwent a lumbar puncture and

additional labs, all of which were normal. (Ex. 1, p. 4.) S.H. was subsequently

transferred back to Kaiser where she underwent additional “rigorous testing” including a

second lumbar puncture, overnight EEG, and MRI, all of which were normal. (Id. at 4-

5.) S.H. was discharged on May 27, 2015. (Id. at 5.)

Petitioner stated that S.H. suffered a fourth seizure, with the same symptoms as

her first three seizures, on May 28, 2015. (Ex. 1, p. 5; see also Tr. 19-23.) S.H. was

first brought to PIH before being transferred to Kaiser where she was diagnosed with

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epilepsy and placed on anti-convulsant medication. (Ex. 1, p. 5.) Petitioner explained

that, at four months, S.H. was able to sit with assistance and had good head control.

(Tr. 21.) However, after starting on phenobarbital, S.H. became extremely groggy and

could no longer lift her head. (Ex. 1, p. 5; see also Tr. 21.) Petitioner described S.H. as

being “lethargic” and “like a zombie.” (Ex. 1, p. 5.) The effect of the loading dose lasted

for about 24 hours before S.H. started to regain some head control, although petitioner

indicated that S.H. still “was not her usual self.” (Tr. 21-22; see also Ex. 1, p. 5.) After

another day, petitioner stated that S.H. remained unusually quiet and unengaging. (Tr.

22.) S.H. continued to take phenobarbital until July 11, 2016. (Ex. 1, p. 5.) While

petitioner indicated that S.H.’s demeanor “improved over months,” she stated that she

did not notice a big difference until after S.H. was fully weaned off the medication. (Tr.

22.) On that point, petitioner testified to the effect that phenobarbital had on S.H.’s

development. (Id. at 23.) She stated that S.H.’s speech was not developing as it

should and that S.H. was stuttering “a lot.” (Id.) After discontinuing the medication,

S.H. has been hitting her milestones despite continuing to stutter. (Id.)

Petitioner stated that S.H. has not suffered any additional seizures since May 28,

2015. (Ex. 1, p. 6.) Petitioner further stated that she sought a second opinion from Dr.

Sarco, who stated that there was a possibility that S.H.’s May 22 vaccinations caused

her seizures. (Id.) After seeing Dr. Sarco, petitioner sought genetic testing for S.H.

from Dr. Loree Willis, the results of which were normal. (Id.)

IV. Expert Opinions

a. Petitioner’s Expert, Marcel Kinsbourne, M.D.5

Petitioner filed a series of expert reports from pediatric neurologist Dr. Marcel

Kinsbourne to support her claim. (See Exs. 7, 24, 28, 45.) Dr. Kinsbourne also

provided testimony at the entitlement hearing, during which he was offered without

objection as an expert in pediatric neurology. (Tr. 31-76.)

5 Dr. Kinsbourne received his Bachelor’s degree from Christ Church College at Oxford University in 1952

and his first medical degree from Oxford University Medical School in 1955. (Ex. 2, p. 1.) He also holds

two other advanced degrees from Oxford, and a second medical degree from the “State of North

Carolina” which was conferred in 1967. (Id.) He is licensed in the United Kingdom, State of North

Carolina, Commonwealths of Massachusetts and Virginia, and by the Medical Council of Canada. (Id.)

He is board certified by the Royal College of Physicians in London, the Educational Council for Foreign

Medical Graduates, and the American Board of Pediatrics. (Id.) Dr. Kinsbourne has held numerous

academic positions throughout his career including professorships and lecturer positions in psychology,

neurology, and pediatrics at Oxford University, the University of Toronto, Harvard Medical School,

Brandeis University, Boston University, Clark University, Tufts University, and the University of Waterloo.

(Id. at 1-3.) He has also held appointments at a similarly broad slate of hospitals including fellowships

and directorships in several areas of neurology at Boston University, the Eunice Kennedy Shriver Center,

and Duke University. (Id.) Dr. Kinsbourne has published extensively on pediatrics, neurology, and

psychology as the primary or supporting author on 425 pieces of peer reviewed medical literature. (Id. at

6-39.)

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i. Dr. Kinsbourne’s initial report

Although S.H. received multiple vaccinations at her four-month well visit, Dr.

Kinsbourne’s initial report discusses only the DTaP vaccine as potentially causal. (Ex.

7.) Dr. Kinsbourne opines that S.H.’s first seizure, which was an afebrile seizure

occurring less than one hour after her DTaP vaccination, was vaccine-caused. (Id. at

2.) He cites two papers to support his general proposition that brief afebrile seizures

can be temporally associated with vaccinations such as the DTaP vaccine. (Id. (citing

Sarah von Spiczak et al., A Retrospective Population-Based Study on Seizures Related

to Childhood Vaccination, 52 EPILEPSIA 1506 (2011) (Ex. 20); D T. Hsieh et al., New-

Onset Afebrile Seizures in Infants, 74 NEUROLOGY 150 (2010) (Ex. 13).) 6 Dr.

Kinsbourne indicates that post-vaccination seizures typically occur within 72 hours of

vaccination, and most often occur within 24 hours of vaccination. (Ex. 7, p. 4.) He

acknowledged that the available epidemiology does not break down data by hour, but

cited one study that observed seizures following the whole cell pertussis vaccine and

noted the shortest interval was one hour. (Id. (citing Jerome V. Murphy, Larrie D. Sarff,

& Kathleen M. Marquardt, Recurrent Seizures After Diphtheria, Tetanus, and Pertussis

Vaccine Immunization, 138 AM. J. DISEASES CHILDREN 908 (1984) (Ex. 18).) He urges

that there is no minimal interval for seizures to occur following pertussis vaccinations.

(Id.)

Further, Dr. Kinsbourne asserts that there is an increased risk of seizures

following receipt of vaccines containing acellular pertussis. (Ex. 7, p. 3.) Relying on a

higher risk of seizures following the older whole cell formulation of the pertussis vaccine,

Dr. Kinsbourne cites several additional studies for the proposition that the acellular

formulation reduced, but did not eliminate, the risk. (Id. (citing Nicole Le Saux et al.,

Decrease in Hospital Admissions for Febrile Seizures and Reports of Hypotonic-

Hyporesponsive Episodes Presenting to Hospital Emergency Departments Since

Switching to Acellular Pertussis Vaccine in Canada: A Report from IMPACT, 112

PEDIATRICS e348 (2003) (Ex. 17); Lisa A. Jackson et al., Retrospective Population-

Based Assessment of Medically Attended Injection Site Reactions, Seizures, Allergic

Responses and Febrile Episodes After Acellular Pertussis Vaccine Combined with

Diphtheria and Tetanus Toxoids, 21 PEDIATRIC INFECTIOUS DISEASE J. 781 (2008) (Ex.

15); M. Miles Braun et al., Infant Immunization with Acellular Pertussis Vaccines in the

United States: Assessment of the First Two Years’ Data From the Vaccine Adverse

Event Reporting System (VAERS), 106 PEDIATRICS 1 (2000) (Ex. 9); Dennis A. Conrad

& Hal B. Jensen, Using Acellular Pertussis Vaccines for Childhood Immunizations:

Potential Benefits Far Outweigh Potential Risks, 105 POSTGRADUATE MED. 1 (1999) (Ex.

6 It should be noted that, while the von Spiczak et al. study identifies some children with afebrile seizures

following vaccination, it does not engage in any statistical analysis of the data. (von Spiczak et al., supra,

at Ex. 20.) The purpose of the paper was only to describe the clinical features of children having reported

seizures or epilepsies that occurred after vaccination. (Id. at 1.) Similarly, the Hsieh et al. paper

examines the presenting characteristics of new-onset afebrile seizures in infants. (Hsieh et al., supra, at

Ex. 13.) It does not discuss vaccines at all, let alone ascribe afebrile seizure activity to vaccines. (Id.)

9

11)).)7 Dr. Kinsbourne opines that the pertussis toxin is toxoided in the acellular

pertussis vaccine; however, some toxoid spontaneously reverts to toxin. (Id. (citing

Michael J. Corbel & Dorothy K. L. Xing, Toxicity and Potency Evaluation of Pertussis

Vaccines, 3 EXPERT REV. VACCINES 89 (2004) (Ex. 12); Chun-Ting Yeun et al., An In

Vitro Assay System as a Potential Replacement for the Histamine Sensitisation Test for

Acellular Pertussis Based Combination Vaccines, VACCINE (2010) (Ex. 23)).) Dr.

Kinsbourne would later disclaim this toxin reversion theory during the hearing. (Tr. 65.)

According to Dr. Kinsbourne, the pertussis toxin “has a selective negative effect

on inhibitory (GABergic) synapses” and can “attach to the G-protein element of neuronal

membrane receptors, setting up a chemical cascade such that the action of inhibitory

neurotransmitters is impaired,” while “the action of excitatory neurotransmitters is

enhanced.” (Ex. 7, p. 3.) This ultimately causes a neurotransmitter imbalance in the

brain that favors excitation, and thus increases the risk of seizure activity. (Id. (citing

Austin Legido et al., Autoimmune and Postinfectious Diseases, CHILD NEUROLOGY

(2006) (Ex. 16)).) Further, he explains that pertussis toxin has an adjuvant effect on the

production of cytokines, including the pro-inflammatory interleukin-1 beta (“IL-1β”),

which has known epileptogenic properties. (Id.)

Dr. Kinsbourne further explains that vaccinations trigger an innate immune

system response, which includes the release of proinflammatory cytokines including IL-

1β. (Ex. 7, p. 3 (citing Xin Chen O.M. Zack Howard, & Joost J. Oppenheim, Pertussis

Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells, 178 J.

IMMUNOLOGY 6123 (2007) (Ex. 10)).) He suggests that, while IL-1β mediates fever, it

also mediates seizures because IL-1β has the propensity to cause seizures and

seizures have the propensity to release additional IL-1β. (Id. (citing Annamaria Vezzani

& Tallie Z. Baram, New Roles for Interleukin-1 Beta in the Mechanisms of Epilepsy, 7

EPILEPSY CURRENTS 45 (2007) (Ex. 22)).) IL-1β receptors are expressed in the

hippocampus, which is a particularly seizure sensitive region of the brain. (Vezzani &

Baram, supra, at Ex. 22.) When IL-1β binds to its receptor, it reduces GABA currents,

which results in diminished inhibition and increased excitability, ultimately decreasing

the subject’s seizure threshold. (Id. (citing Natalie T. Sanon, Sebastien Desgent, &

Lionel Carmant, Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual

7 It has been observed in prior cases, however, that these studies do not support Dr. Kinsbourne’s

assertion because they do not confirm whether the much lower incidences of seizures following acellular

pertussis remain above background rates. See, e.g. Bangerter ex rel. D.B. v. Sec’y of Health & Human

Servs., No. 15-1186V, 2022 WL 439535, at *21-23 (Fed. Cl. Spec. Mstr. Jan. 18, 2022); Vinesar v. Sec’y

of Health & Human Servs., No. 18-440V, 2023 WL 5427935, at *28-31 (Fed. Cl. Spec. Mstr. July 28,

2023), motion for review filed (Oct. 1, 2023). As Dr. Kinsbourne highlighted by his citation to Hsieh et al.,

childhood seizures occur most commonly in infancy (up to 24 months of age) irrespective of vaccination.

(Hseih et al., supra, atEx. 13, pp. 2-3.) In his second report, Dr. Kinsbourne added a further citation to a

study by Uberall et al. (Ex. 24, p. 2 (citing See M.A. Uberall et al., Severe Adverse Events in a

Comparative Efficacy Trial in Germany in Infants Receiving Either the Lederle/Takeda Acellular Pertussis

Component DTP (DTaP) Vaccine, the Lederle Whole-Cell Component DTP (DTP) or DT Vaccine. The

Pertussis Vaccine Study Group., 89 DEV. BIOLOGY STANDARDIZATION 83 (1997) (Ex. 25)).) However, only

the abstract was filed. The abstract is limited to indicating that convulsions within three days of the DTaP

vaccine were five times lower than with the whole cell DTP vaccine. (Uberall et al., supra, at Ex. 25.)

10

Pathology, 2012 EPILEPSY RES. & TREATMENT 1 (2012) (Ex. 19)).) Dr. Kinsbourne

explains that, among those whose “GABergic neurons [are] already compromised, as in

some SCN1A mutations in children,” this can result in seizures.8 (Id.)

ii. Dr. Kinsbourne’s first supplemental report

In his second report, Dr. Kinsbourne primarily addresses Dr. Holmes’ assertion

that S.H. suffered paroxysmal events rather than seizures. He confirms the five specific

events he concludes were seizures: May 22, 2015 at about 10:30am9 (Ex. 24, p. 1

(citing Ex. 6, pp. 3-6, 8-9)); May 22, 2015, at 3:50PM (Id. (citing Ex. 6, pp. 3-6, 8-9, 19-

20)); May 26, 2015 (two seizures) (Id. (citing Ex. 6, pp. 52-53)); and May 28, 2015 (Id.

(citing Ex. 6, pp. 109-11)). Dr. Kinsbourne stresses that the treating physicians

considered S.H.’s events to be seizures and indicates that his review of the literature

failed to confirm a postictal period as a diagnostic requirement for a generalized seizure.

(Id.) To the extent Dr. Holmes cited a comment by Dr. Fuqua doubting that S.H. was

experiencing seizures, Dr. Kinsbourne indicates the comment was in relation to

separate “subacute spells” and not the events he has identified as seizures.10 (Id. at 2

(discussing Ex. 4, pp. 77-79).)

Dr. Kinsbourne further opines that S.H.’s seizures meet the criteria for epilepsy.

(Ex. 24, p. 2.) Additionally, he opines that, because the first two onset seizures were

caused by the DTaP vaccine, “and the subsequent seizures were similar in nature to the

onset seizures, it follows that the vaccinations triggered [S.H.]’s epilepsy.” (Id.) Dr.

Kinsbourne reiterated his reliance on a heightened incidence of post-DTaP seizures

among children with SCN1A genetic variants. (Id.)

iii. Dr. Kinsbourne’s second supplemental report

Dr. Kinsbourne’s third report (Ex. 28) answered several follow up questions

posed by my October 9, 2020 order. (See ECF No. 41.) Dr. Kinsbourne was asked to

explain why his opinion offered in this case was not incompatible with the opinion he

8 The SCN1A gene variant causes a syndrome that is known as “Dravet syndrome.” This gene variant

and the resulting Dravet syndrome have been the subject of many prior decisions within this program.

See, e.g., Vinesar, 2023 WL 5427935; Thompson v. Sec’y of Health & Human Servs., No. 15-671V,

2023 WL 21234 (Fed. Cl. Spec. Mstr. Jan 3, 2023); Oliver v. Sec’y of Health & Human Servs., No. 10-

394V, 2017 WL 747846 (Fed. Cl. Spec. Mstr. Feb. 1, 2017), aff’d, 133 Fed. Cl. 341 (2017), aff’d, 900 F.3d

1357 (Fed. Cir. 2018); Faoro v. Sec’y of Health & Human Servs., No. 10-704V, 2016 WL 675491 (Fed. Cl.

Spec. Mstr. Jan. 29, 2016), motion for review denied, 128 Fed. Cl. 61 (2016); Barclay v. Sec’y of Health &

Human Servs., No. 07-605V, 2014 WL 7891493 (Fed. Cl. Spec. Mstr. Dec. 15, 2014), motion for review

denied, 122 Fed. Cl. 189 (2015). There is no evidence in this case that S.H. carries this type of gene

variant or suffers this syndrome.

9 Regarding Dr. Holmes’s emphasis on the significance of postictal periods, Dr. Kinsbourne interprets a

notation that “she was a little bit sleepy” following the event as a postictal period. (Ex. 24, p.1.)

10 I do note that Dr. Kinsbourne further addressed some of these points in his fourth report. (See Ex. 45,

p. 2.) However, it is not necessary to separately summarize this aspect of the later report.

11

offered in a prior case, Fuller ex rel. B.F. v. Secretary of Health and Human Services.

(Id. (citing No. 15-1470V, 2019 WL 7576382, at *8-9 (Fed. Cl. Spec. Mstr. Dec. 17,

2019).) In that case, Dr. Kinsbourne appeared to opine that fever itself is implicated in

the process by which vaccines can cause seizures and further that it is complex11 febrile

seizures that can result in epilepsy. (Id. (discussing Fuller ex rel B.F., 2019 WL

7576382).)

Dr. Kinsbourne cited three studies to demonstrate that the effects of IL-1β in

causing fever and seizure are distinct despite often occurring concurrently. (Ex. 28, pp.

1-2 (citing C. Dube, et al., Commentary, Cytokines: A Link Between Fever and

Seizures, 5 EPILEPSY CURRENTS 169 (2005) (Ex. 33); Celine Dube et al., Interleukin-1β

Contributes to the Generation of Experimental Febrile Seizures, 57 ANNALS NEUROLOGY

152 (2005) (Ex. 48); Vezzani & Baram, supra, at Ex. 22).) Dr. Kinsbourne agreed that

complex seizures are more likely to lead to epilepsy. (Id. at 2.) He indicated that the

risk of future unprovoked seizures following a simple febrile seizure is 2.5% compared

to a 1.4% risk among the general population whereas the risk of future unprovoked

seizures following complex febrile seizures is between 6-49% depending on additional

factors. (Id. at 3.) Dr. Kinsbourne opined that S.H.’s initial onset seizure had focal

features and recurred within 24 hours and was therefore complex, although it was not

accompanied by an elevation in temperature. (Id.) During the hearing, Dr. Kinsborne

would instead later acknowledge that S.H.’s seizures were generalized clonic-tonic

seizures. (Tr. 33, 60.)

Dr. Kinsbourne was also prompted to substantiate two additional points raised by

his prior reports. (ECF No. 41, pp. 1-2.) First, he was directed to substantiate, vis-à-vis

his comparison between the relative risk of seizures following whole cell versus acellular

pertussis vaccine, that the lower incidences of post-DTaP seizures remained above

either control or background rates. (Id.) He confirmed that he cannot and that he

therefore is “not in a position to rely on epidemiologic evidence on this issue.” (Ex. 28,

p. 4.) Additionally, Dr. Kinsbourne cited heightened seizure activity among SCN1A

gene variant carriers without supporting literature or explaining how the assertion is

relevant to S.H. given his acknowledgement that she does not carry that gene variant.

(ECF No. 41, p. 2.) Dr. Kinsbourne discussed studies that he indicated show that, while

Dravet syndrome patients are at “striking liability to febrile seizures,” a significant portion

of post-DTaP seizure onset in Dravet syndrome occurred via afebrile seizures. (Ex. 28,

p. 4.) Combined with an additional study by Berg et al., Dr. Kinsbourne asserts that this

is relevant to S.H.’s case because it shows that “children whose seizures occur with

relatively low fever grades require less provocation to have a seizure than do those

whose initial seizures occurred at higher temperatures.” (Id. at 5 (citing Anne T. Berg et

al., Predictors of Recurrent Febrile Seizures: A Prospective Cohort Study, 151 ARCHIVES

PEDIATRIC & ADOLESCENT MED. 371 (1997) (Ex. 29).) Therefore, because the medical

literature supports the notion that Dravet syndrome patients experience afebrile

11 Dr. Kinsbourne explains that for generalized seizures, simple febrile seizures are considered

uncomplicated convulsions that persist for less than 10-15 minutes. (Ex. 28, pp. 2-3.) Complex seizures

are those that last longer. For partial afebrile seizures are complex if there is a loss of consciousness and

simple if not. (Id.) The terms simple and complex are applied only to febrile seizures. (Ex. D, p. 3.)

12

seizures due to having a lowered seizure threshold, “S.H.’s afebrile seizure onset during

infancy simply indicates that she had a lower than usual seizure threshold at that early

stage in her development.” (Id. at 6.)

iv. Dr. Kinsbourne’s third supplemental report

In his fourth report, Dr. Kinsbourne revised his opinion to indicate that he

believes that S.H.’s condition could also have been caused by her Prevnar 13 vaccine

either alone or in combination with her DTaP vaccination. (Ex. 45, p. 3.) Dr.

Kinsbourne cites additional studies for the proposition that the Prevnar 13 vaccine has

been associated with increased risk of febrile seizures.12 (Id. (citing Robert P. Wise et

al., Postlicensure Safety Surveillance for 7-Valent Pneumococcal Conjugate Vaccine,

292 JAMA 1702 (2004) (Ex. 53); Jonathan Duffy et al., Febrile Seizure Risk After

Vaccination in Children 6 to 23 Months, 138 PEDIATRICS (2016) (author manuscript) (Ex.

50); Meghan A. Baker, et al., The Risk of Febrile Seizures Following Influenza and 13-

Valent Pneumococcal Conjugate Vaccines, 38 VACCINE 2166 (2020) (Ex. 46)).) He also

reiterated his assertion that the reduction in seizures following the change from DTP to

DTaP vaccination evidences that the DTaP vaccine causes seizures. (Id.) He asserts

that “[m]any studies have shown that vaccinations cause seizures and many of those

studies had appropriate controls.” (Id.) As an example, he cites Sun et al., which

showed an increased incidence of febrile seizures following DTaP vaccination. (Id.

(citing Yuelian Sun et al., Risk of Febrile Seizures and Epilepsy After Vaccination with

Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus

Influenzae Type B, 307 JAMA 823 (2012) (Ex. 21).) Dr. Kinsbourne further cites Wang,

et al., for the proposition that there is an increased risk of seizures one day following

both DTaP and Prevnar 13 vaccines. (Id. at 4 (citing Shirley V. Wang et al.,

Determining Which of Several Simultaneously Administered Vaccines Increase Risk of

an Adverse Event, 43 DRUG SAFETY 1057 (2020) (Ex. 52).) Importantly, the Wang study

does not specifically implicate afebrile seizures but merely fails to distinguish between

febrile and afebrile seizures. (Wang et al., supra, at Ex. 52.)

Dr. Kinsbourne reiterates his reliance on research from Vezzani group to support

that idea that “the flow of cytokines to the hypothalamic control center for temperature

and the flow of cytokines to hippocampal and neocortical seizure generators are

independent of each other.” (Ex. 45, p. 4 (citing Vezzani & Baram, supra, at Ex. 22).)

He further opines that “the lower the seizure threshold is, the less inflammation it takes

to provoke a seizure.” (Id.) He stresses the findings of the study by Dube et al., which

he asserts support the idea that fever “usually accompanies the seizure but does not

cause it.” (Id. at 5 (citing Dube, et al., supra, at Ex. 33).) He summarized his opinion as

follows:

12 Dr. Kinsbourne also notes that 19 cases of afebrile seizure following Prevnar were noted in the Wise

study. (Ex. 45, p. 3 (citing Wise et al., supra, at Ex. 53, p. 6).) Importantly, however, the authors do not

ascribe causation. Remarking on the total number of reported seizures – the majority of which were

febrile – they note that “[l]ike other vaccines, PCV can provoke fever, which could trigger a febrile

seizure.” (Wise et al., supra Ex. 53, p. 8.)

13

[S.H.] probably had a lower-than-normal seizure threshold before she

received her May 22, 2015 vaccination and the vaccinations further lowered

the threshold to the tipping point. This conclusion is based on: 1. the fact

that she had seizures at all; 2. that she had a seizure so quickly after the

vaccinations; and 3. that she had a seizure without a clear fever. It suggests

that [S.H.] was on the edge and only needed a small nudge to go over the

edge (and have a seizure).

(Id.at 5-6.) Dr. Kinsbourne further opined that each seizure produces more

inflammatory cytokines and, therefore, S.H.’s subsequent seizures were due at least in

part to the inflammation resulting from her first seizures. (Id. at 6.) Accordingly, “[s]ince

the vaccination caused the first seizure it was a substantial factor in the cause of them

all.” (Id.)

v. Testimony

At the entitlement hearing, Dr. Kinsbourne testified that S.H. experienced

generalized tonic-clonic seizures “[w]ithout any doubt.” (Tr. 33.) He further testified that

“there is a somewhat disproportionate risk of seizure activity within a day” of receiving

the acellular pertussis vaccine, pneumococcal vaccine, “or both.” (Id. at 36.) However,

he noted that afebrile seizure following vaccination is “fairly unusual” in young children

and does not “rise to a level that will be picked up in epidemiological studies.”13 (Id. at

36.) Dr. Kinsbourne acknowledged that the seizure threshold in young children is

generally “fairly low,” and it can be so low in some cases that onset of seizure activity

can precede fever or occur in the absence of fever. (Id. at 38.) He explained that this is

because the fever does not usually generate the seizure. (Id.) Instead,

proinflammatory cytokines, which are released by vaccinations, cause both the fever

and the seizure “by influencing the function of two different parts of the brain.” (Id.)

He further testified that, in the case of vaccine-caused seizure activity, onset

often occurs within “a matter of hours,” and that there is “no way of rationalizing” the

concept that onset could be too soon to be vaccine caused. (Tr. 48.) Although he

recognized that it takes time for the body to create proinflammatory cytokines in

response to vaccination, Dr. Kinsbourne explained that how much time it takes for fever

to set in is irrelevant to this case as any fever would be a “byproduct” of the process by

which a vaccine can cause a seizure. (Id. at 49.)

Dr. Kinsbourne testified that S.H. likely had a low seizure threshold based on the

abruptness of onset and the lack of any documented fever. (Tr. 45.) He analogized

S.H.’s course to that of an infant with an SCN1A gene variation because children with

this gene are prone to afebrile seizures triggered by their 4-month vaccinations. (Id. at

43.) Though he acknowledged that S.H. does not have any genetic abnormalities that

would cause her to be particularly susceptible to seizures, Dr. Kinsbourne suggested

13 During the hearing, Dr. Kinsbourne specifically disavowed his claim in his earlier reports that the

pertussis toxoid in the DTaP vaccine can spontaneously revert to pertussis toxin. (Tr. 64-65.) This

assertion had informed his interpretation of the epidemiologic data.

14

that onset was so rapid that “one can’t imagine any other interfering process that could

have caused” the seizures. (Id. at 43.) However, in response to the undersigned’s

questions, Dr. Kinsbourne indicated that S.H.’s course could not ultimately be

distinguished from benign epilepsy of childhood, apart from onset of multiple seizures

having occurred on the day of vaccination. (Id. at 75.)

Dr. Kinsbourne explained that the seizures themselves lower the seizure

threshold and make subsequent events more likely. (Tr. 52.) In essence, he testified

that “seizure begets seizure,” such that the occurrence of one seizure changes the brain

in a way that favors another seizure occurring and so on. (Id. at 69-70.) He further

explained that epilepsy is a self-sustaining process whereby one does not require a

trigger for seizure activity to occur. (Id. at 72.) Dr. Kinsbourne testified that it is

customary to keep a child on anti-seizure medication until they have been free from

seizures for at least a year. (Id. at 52-53.) He acknowledged that there is no record

that supports the contention that S.H. suffered any adverse effects as a result of taking

phenobarbital. (Id. at 57.) However, Dr. Kinsbourne testified that discontinuing

phenobarbital without any subsequent seizures is what represents confirmation of

epilepsy remission. (Id. at 70.)

b. Respondent’s Expert, Gregory Holmes, M.D. 14

In support of his position, respondent filed several expert reports by pediatric

neurologist Dr. Gregory Holmes. (Exs. A, C, D.) Dr. Holmes also provided testimony at

the entitlement hearing, during which he was offered without objection as an expert in

pediatric neurology, with an additional specialty in seizure disorders. (Tr. 77-129.)

i. Dr. Holmes’ initial report

Dr. Holmes opines that what petitioner describes as seizures were actually

“paroxysmal events of unknown etiology.” (Ex. A, p. 10.) He does not believe that “[t]he

semiology of the events” is suggestive of epilepsy and emphasizes the fact that there

has been no corroborative testing indicating an epileptic condition. (Id.) Dr. Holmes

notes that the first event ended with S.H. crying, whereas generalized seizure disorder

14

Dr. Holmes received his bachelor’s degree from Washington & Lee University in 1970, and his medical

degree from the University of Virginia in 1974. (Ex. B, p. 1.) Dr. Holmes also received an honorary

medical degree from Harvard University in 1996. (Id.) Dr. Holmes served as an intern and resident in

pediatrics at Yale University School of Medicine from 1974 to 1976 before moving on to the University of

Virginia School of Medicine to serve as a resident in pediatric neurology from 1976 to 1979. (Id.) He is

licensed in Connecticut, Georgia, Massachusetts, New Hampshire, and Vermont, and board certified by

the American Boards of Pediatrics, Psychiatry and Neurology, and Clinical Neurophysiology. (Id.) Dr.

Holmes has held professorships in Neurology and Pediatrics at the University of Connecticut, the Medical

College of Georgia, Harvard Medical School, Dartmouth Medical School, and the University of Vermont

College of Medicine. (Id. at 2.) He has served as a staff neurologist and director of various neurology

and neurophysiology labs at eight different hospitals in five different states, including at the Children’s

Hospital of Boston, Massachusetts and the Dartmouth-Hitchcock Medical Center in New Hampshire. (Id.)

Dr. Holmes has contributed to 312 pieces of peer-reviewed medical literature on pediatrics and neurology

as either the sole, primary, or supporting author. (Id. at 40-65.)

15

“inevitably is associated with postictal unresponsiveness or stupor.” (Id. at 10-11.) The

second event, which was observed by hospital staff, also lacked a postictal state. (Id.)

According to Dr. Holmes, the lack of a postictal state following alleged convulsions

“argues strongly against an epileptic event.” (Id. at 11 (citing Makram Obeid &

Mohamad A. Mikati, Expanding Spectrum of Paroxysmal Events in Children: Potential

Mimickers of Epilepsy, 37 PEDIATRIC NEUROLOGY 309 (2007) (Ex. A, Tab 1)).) Dr.

Holmes also highlights S.H.’s EEG results, explaining that it is very unlikely for an infant

with epilepsy to be monitored for two 24-hour periods without any signs of epilepsy or

seizure.15 (Id.; see also Tr. 91.) Further, paroxysmal events in children may mimic

epileptic seizures and are only now being more widely recognized; nonepileptic

paroxysms may present with drop attacks, limb or eye jerks, and abnormal postures.

(Ex. A, p. 11 (citing Obeid & Mikati, supra, at Ex. A, Tab 1).) Dr. Holmes submits that

there is no indication in the medical record that S.H.’s vaccinations were in any way

related to her paroxysms which were, by Dr. Holmes’ description, a “benign, self-

resolving condition.” (Id.)

Dr. Holmes explains that a link between DTaP and seizures has not yet been

discovered with any certainty and cites an Institute of Medicine (“IOM”) Review of

Adverse Effects of Vaccines, which noted that the available studies alleging any such

link were not rigorous enough to be reliable. (Ex. A, p. (citing COMM. TO REV. ADVERSE

EFFECTS OF VACCINES, INST. OF MED., ADVERSE EFFECTS OF VACCINES: EVIDENCE AND

CAUSALITY (Kathleen Stratton et al. eds., 2012) (Ex. A, Tab 9) [hereinafter IOM review].)

Further, the IOM found no evidence connecting the mechanisms of seizures or epilepsy

to any of the vaccines that S.H. received. (Id.) The only study that the IOM perceived

as methodologically sound failed to identify an increased risk of seizures in DTaP

vaccinated infants 6 weeks to 23 months. (Id. at 11-12 (citing Wan-Ting Huang et al.,

Lack of Association Between Acellular Pertussis Vaccine and Seizures in Early

Childhood, 126 PEDIATRICS e263 (2010) (Ex. A, Tab 12)).)

Dr. Holmes explains that the primary study cited in Dr. Kinsbourne’s first report to

support a temporal relationship between vaccinations and seizures was not particularly

rigorous and amounted to a retrospective review of a case report database of adverse

events without any sort of non-immunized control group. (Ex. A, p. 12 (citing von

Spiczak, supra, at Ex. 20).) Dr. Holmes reiterates the IOM findings that virtually all of

the available epidemiological studies either had similar issues in that they came from

passive surveillance programs and lacked control groups, had “serious methodological

limitations,” or combined coma and seizure symptoms in the analysis and failed to

properly explain how cases were selected. (Id. (citing IOM review, supra, at Ex. A, Tab

15 Dr. Holmes acknowledges that children can have epilepsy with normal EEGs, but that such results

make the likelihood of epilepsy “quite low.” (Ex. A, p. 12 (citing Pradeep N. Modur & Barbara Rigdon,

Diagnostic Yield of Sequential Routine EEG and Extended Outpatient Video-EEG Monitoring, 119

CLINICAL NEUROPHYSIOLOGY 190 (2008) (Ex. A, Tab 15); Elaine Wirrell et al., Ambulatory

Electroencephalography (EEG) in Children: Diagnostic Yield and Tolerability, 23 J. CHILD NEUROLOGY 655

(2008) (Ex. A, Tab 16); S.J.M. Smith, EEG in the Diagnosis, Classification, and Management of Patients

with Epilepsy, 76 J. NEUROLOGY NEUROSURGERY & PSYCHIATRY ii2 (2005) (Ex. A, Tab 17); Audrey Riquet

et al., Usefulness of Video-EEG Monitoring in Children, 20 SEIZURE 18 (2011) (Ex. A, Tab 18)); see also

Tr. 91.)

16

9).) Dr. Holmes explains that the Sun study cited by Dr. Kinsbourne fails to support

petitioner’s claim because it focuses on an increased risk in febrile seizures while S.H.

did not experience seizures, and if she did, they were certainly not febrile. (Id. at 13

(citing Sun et al., supra, at Ex. 21).)

Finally, Dr. Holmes questions Dr. Kinsbourne’s proposed theory. Dr. Holmes

explains that, in referencing the evidence he cited to explain how pertussis toxin can

facilitate increased seizure activity, Dr. Kinsbourne fails to include a passage that reads:

Whereas in the vast majority of cases the blood-brain barrier prevents entry

of the toxin into the brain, its temporary disruption with a concomitant viral

disease or fever or a response to the endotoxin present in the vaccine could

well facilitate access of pertussis toxin to the nerve cells. Such a disruption

has been seen in pertussis encephalopathy, in which high CSF antibody

titers to pertussis toxin have been demonstrate[d].

(Ex. A, p. 12 (quoting Legido et al., supra, at Ex. 16, p. 3).) Dr. Holmes notes that S.H.

did not have a viral illness, fever, or pertussis encephalopathy. (Id.) Further, Dr.

Holmes writes that there is no evidence that the endotoxin found in attenuated pertussis

vaccines alters G-protein coupled receptors or inactivates G-proteins. (Id. at 12-13.)

Dr. Holmes also points out that Dr. Kinsbourne relied on a passage from the Legido

chapter, which states that initial seizures occur within 24 hours of immunization;

however, this passage, when taken in context, refers to whole-cell pertussis

vaccinations and to those patients who developed epileptic encephalopathy, severe

myoclonic epilepsy, or Lennox-Gastaut syndrome, none of which apply to S.H. (Id.

(citing Legido et al., supra, at Ex. 16).)

ii. Dr. Holmes’ first supplemental report

In his second report, Dr. Holmes notes that despite the fact that treating

physicians recorded the first events as seizures, S.H.’s presentation is nonetheless

inconsistent with generalized seizures and that observations of treating physicians do

not amount to diagnostic certainty. (Ex. C, pp. 1-2.) Further, Dr. Holmes contests that

the diagnosis of epilepsy does not require simply two or more recurrent seizures, but

two or more unprovoked seizures, which did not occur in S.H.’s case. (Id. at 2.) He

notes that Dr. Kinsbourne incorrectly claims that because S.H.’s vaccinations triggered

her first two seizures, and because her subsequent episodes were similar in nature to

the first two, it follows that her subsequent episodes were also caused by her

vaccinations. (Id.) According to Dr. Holmes, there are a “myriad of ‘triggers’” for

seizures; however, none of these triggers are said to cause epilepsy. (Id.) Finally, Dr.

Holmes points out that the Uberall study cited by Dr. Kinsbourne lacked an appropriate

control group and, to the extent that the study is informative, reported an “incredibly low”

convulsion rate within 3 days of DTaP vaccination. (Id. at 3 (citing M.A. Uberall et al.,

supra, at (Ex. 25)).)

17

iii. Dr. Holmes’ second supplemental report

Dr. Holmes’ third report primarily addresses whether fever is part of the causal

mechanism for post-vaccinal seizures. (Ex. D, p. 1.) He agrees that fever is triggered

by pyrogens, which can be exogenous or endogenous, and that endogenous pyrogens

include cytokines that are released by immune cells. (Id.) Dr. Holmes explains that,

while these pyrogens act to increase body temperature, they also trigger receptors in

the preoptic nucleus in the brain, which releases cytokines into the hypothalamus to set

a new target temperature. (Id.) However, he disagrees that cytokines produced in the

thigh following a DTaP vaccination can enter the brain in a manner and amount

sufficient to produce a seizure. (Id.) Dr. Holmes writes that, in order for cytokines to

activate central microglia, they need to cross the blood brain barrier, a regulatory

interface in response to cytokines. (Id. at 2.) The amount of blood-borne cytokines

crossing the blood brain barrier is “quite low,” calculated at about .08% of the serum

concentration. (Id. (citing W.A. Banks et al., Human Interleukin (IL) 1α, Murin IL-1α and

Murine IL-1β are Transported from Blood to Brain in the Mouse by a Shared Saturable

Mechanism, 259 J. PHARMACOLOGY & EXPERIMENTAL THERAPEUTICS 988 (1991) (Ex. D,

Tab 4)).) Studies have shown that there are limited pathways for the cytokines to travel

past the blood brain barrier, and that these pathways only lead to specific areas, such

as the hypothalamus, which are not known to generate seizures, and thus, the

likelihood that cytokines generated in response to vaccination would cause a seizure is

“miniscule.” (Id. (citing Ning Quan, In-Depth Conversation: Spectrum and Kinetics of

Neuroimmune Afferent Pathways, 40 BRAIN BEHAVIOR & IMMUNITY 1 (2014) (Ex. D, Tab

5)).) S.H. did not suffer from a fever after her immunization, which suggests that the

immune response was not robust and makes it even less likely that her alleged seizures

were immune-mediated. (Id.)

Dr. Holmes clarifies that cytokines are used by the central nervous system as

neurotransmitters during central nervous system infection, trauma, and following

seizures; however, the increase in cytokines associated with seizures is a response to

the seizure, not the cause. (Ex. C, p. 2 (citing Gang Li et al., Cytokines and Epilepsy,

20 SEIZURE 249 (2011) (Ex. D, Tab 7)).) Dr. Holmes contends that Dr. Kinsbourne’s

reliance on the Dube study is misguided because the study utilized “very high,

nonphysiologic doses” of IL-1β injected directly into the ventricles of the brain. (Id.) Dr.

Holmes emphasizes that the amount of cytokines required to effectively lower the

seizure threshold and generate afebrile seizures in the Dube study was more than 1000

times the amount recorded in humans following vaccination. (Id. (citing Dube et al.,

supra, at Ex. 48; Yasuyo Kashiwagi et al., Production of Inflammatory Cytokines in

Response to Diphtheria-Pertussis-Tetanus (DPT), Haemophilus Influenzae Type B

(Hib), and 7-Valent Pneumococcal (PCV7) Vaccines, 10 HUM. VACCINES &

IMMUNOTHERAPEUTICS 677 (2014) (Ex. D, Tab 13)).)

Dr. Holmes explains that most febrile seizures are generalized tonic-clonic

seizures, while 30 to 35% have one or more of the following complex features: focal

onset, lasting longer than 10 minutes, or multiple seizures during an illness episode.

(Ex. D, p. 2.) One specific type of seizure, febrile status epilepticus, is characterized by

18

seizures lasting longer than 30 minutes and is the only type of seizure known to

contribute to epilepsy. (Id. (citing Miquel Raspall-Chaure et al., Outcome of Paediatric

Convulsive Status Epilepticus: A Systematic Review, 5 LANCET NEUROLOGY 769 (2006)

(Ex. D, Tab 14)).) Dr. Holmes explains that “simple” and “complex” are only used to

distinguish febrile seizures, which S.H. did not have. (Id. at 3 (citing Anne T. Berg et al.,

Revised Terminology and Concepts for Organization of Seizures and Epilepsies: Report

of the ILAE Commission on Classification and Terminology, 2005–2009, 51 EPILEPSIA

676 (2010) (Ex. D, Tab 15)).) Dr. Holmes explains that S.H.’s medical records contain

descriptions of symptoms consistent with generalized and focal seizures, and that in

infants, seizures are usually consistent and manifest in the same way. (Id.) Thus, the

variety of presentations, as well as the normal EEGs, suggest that S.H.’s episodes were

not epileptic in nature. (Id.)

Dr. Holmes addresses Dr. Kinsbourne’s reliance on studies of children with

Dravet syndrome to suggest that children with especially low seizure thresholds may

suffer afebrile seizures as a result of peripheral cytokine production following

vaccination. (Ex. D, pp. 3-4.) Dr. Holmes suggests that if this were the case, then

S.H.’s subsequent DTaP vaccinations would have also triggered seizures due to the

fact that they elicit the same cytokine response argued to have caused S.H.’s seizures.

(Id. at 4.) Further, there is no evidence that S.H. was in fact more susceptible to

seizures. (Id.) Dr. Holmes suggests that the cited literature, which involves subjects

with Dravet syndrome, with a SCN1A mutation, or who experienced febrile seizures, is

not relevant in this case. (Id.)

Finally, Dr. Holmes submits that S.H.’s updated medical records do not suggest

that she has epilepsy. (Ex. D, pp. 4-5.) Even if the events were seizures, Dr. Holmes

indicates that they “did not cause any harm.” (Id. at 4.)

iv. Dr. Holmes’ third supplemental report

Dr. Holmes’ final report notes that Dr. Kinsbourne’s reliance on the Wise study is

misguided due to the fact that it involved a passive reporting system of cases which

“frequently defy facile assessment of whether vaccinations played a causal role since

no information from non-vaccinated controls [are] included,” as, without the control

group, “it is impossible to say whether the vaccine increased the risk of convulsions” in

this study’s subjects. (Ex. G, p. 1 (citing Wise et al., supra, at Ex. 53).)

Dr. Holmes criticizes Dr. Kinsbourne’s independent pathways theory as a

misinterpretation and inappropriate extrapolation of the cited medical literature. (Ex. G,

p. 2.) He further argues that there is no evidence that S.H. had a cytokine-induced

inflammatory process that impacted the hypothalamic control center and hippocampal

seizure generators. (Id.) He notes that S.H. did not have a fever or show any signs of

seizure or epilepsy during objective testing. (Id.)

19

v. Testimony

To support his position that S.H. was experiencing some type of paroxysmal

event, Dr. Holmes pointed to petitioner’s observation of S.H. opening and closing her

mouth during the episode as not being typically associated with generalized tonic-clonic

seizures. (Tr. 89-90.) Instead, he suggested that tensing of the jaw and “twitching” of

the mouth are generally observed. (Id. at 90.) He reiterated his concerns about S.H.’s

24-hour EEGs, which rendered normal results, before ultimately acknowledging that “a

normal EEG does not rule out a seizure disorder.” (Id. at 91.) Although he maintained

that S.H.’s events were likely not seizures, Dr. Holmes conceded that, if the events were

seizures, then S.H. had epilepsy, which he explained is quite common in children. (Id.

at 87-94, 119-120.) He described a benign childhood epilepsy course that is commonly

referred to as “smooth sailing epilepsy” where children respond well to medications,

have a benign course, and have normal neural development and testing. (Id. at 119.)

He acknowledged that placing S.H. on phenobarbital was a reasonable medical

decision and agreed with Dr. Kinsbourne that S.H. was considered to be in remission of

epilepsy when the phenobarbital was successfully discontinued. (Id. at 87, 117-24.) Dr.

Holmes clarified that, prior to being taken off phenobarbital, S.H. was considered “under

seizure control,” and the medical community does not know for certain whether the

medication is preventing further seizures. (Id. at 122-24.) The only indication of the

efficacy of the medication is evidence that it is not working, i.e., the child continues to

have seizures while on medication. (Id. at 123.) For this reason, the decision to wean a

child off anti-seizure medication is a clinical judgment that is based on the specific

child’s medical history and after “a long discussion” with the parents. (Id. at 124.)

Dr. Holmes testified that there is no evidence that the subject vaccines can cause

afebrile seizures or that S.H. had an inherently low seizure threshold or compromised

blood brain barrier prior to her initial seizures. (Tr. 96, 101.) He explained that the

literature concerning Dravet syndrome is not relevant to this case as S.H. does not have

Dravet syndrome and did not experience febrile seizures. (Id. at 97, 107-08.)

Regarding Dr. Kinsbourne’s assertion that seizures beget seizures, Dr. Holmes

explained that there is no evidence to support this assertion and that the theory of

kindling has been discarded by the medical community. (Id. at 98-100, 113-15, 124-25.)

Dr. Holmes acknowledged that seizures can cause brain inflammation and the release

of cytokines; however, he testified that there is no evidence that a few short seizures

can increase cytokine production to the point of causing brain damage or a chronic

seizure disorder. (Id. at 99-100, 103.)

Dr. Holmes clarified that a febrile seizure is caused by the fever itself. (Tr. 106-

07.) Although he acknowledged that children are prone to febrile seizures at lower

temperatures, he explained that fever requires a temperature of at least 100.4 degrees

Fahrenheit. (Id. at 107, 110.) Thus, a child with temperature that is elevated but still

lower than 100.4 degrees Fahrenheit when a seizure occurs is not experiencing a

febrile seizure. (Id. at 107-08.) Dr. Holmes explained that vaccinations can trigger fever

by releasing cytokines at the injection site that then travel up a signaling pathway to the

hypothalamus. (Id. at 112.) The fever then activates neurons and opens ion channels,

20

leading to neuron depolarization and, ultimately, to seizure. (Id.) In S.H.’s case, there

was no objective evidence of brain inflammation, as demonstrated by the test results or

by the presence of fever, and no evidence that any brain inflammation lasted long

enough to cause subsequent seizures. (Id. at 100-01.)

c. Respondent’s Expert, Herman Staats, Ph.D. 16

Respondent also filed expert reports from pathologist/immunologist Dr. Herman

Staats. (Exs. E, H.) Dr. Staats provided additional testimony at the entitlement hearing.

(Tr. 130-158.)

i. Dr. Staats’ initial report17

Dr. Staats’ outlines the innate and adaptive immune responses to vaccinations.

(Ex. E, p. 2.) He explains that the innate immune response occurs rapidly, within

minutes to hours after vaccinations, and is activated by exposure to vaccine adjuvants,

such as alum, or pathogen components that activate conserved receptors in the

immune system, such as toll-like receptors (“TLR”), that recognize pathogen-associated

molecular patterns (“PAMPs”) produced by microbes. (Id.) Cells of the innate immune

system respond to PAMPs by secreting cytokines, which recruit other immune cells to

the immunization site. (Id. (citing David Vermijlen & Immo Prinz, Ontogeny of Innate T

Lymphocytes – Some Innate Lymphocytes are More Innate Than Others, 5 FRONTIERS

IMMUNOLOGY, 1 (2014) (Ex. E, Tab 2); Karen Smith Korsholm et al., T-Helper 1 and T-

Helper 2 Adjuvants Induce Distinct Differences in the Magnitude, Quality and Kinetics of

the Early Inflammatory Response at the Site of Injection, 129 IMMUNOLOGY 75 (2009)

(Ex. Ex, Tab 7); Isme De Kleer et al., Ontonlogy of Myeloid Cells, 5 FRONTIERS

IMMUNOLOGY, 1 (2014) (Ex. E, Tab 6)).) These cytokine responses vary by vaccination

but typically return to baseline levels within 1 to 7 days after vaccination. (Id. (citing

William M. Gwinn et al., A Comparison of Non-Toxic Vaccine Adjuvants for Their Ability

to Enhance the Immunogenicity of Nasally-Administered Anthrax Recombinant

Protective Antigen, 31 VACCINE 1480 (2013) (Ex. E, Tab 10); Jacob T. Minang et al.,

Enhanced Early Innate and T Cell-Mediated Responses in Subjects Immunized with

16

Dr. Staats received his bachelor’s degree in medical technology from Salisbury University in 1988 and

his PhD in microbiology and immunology from the University of South Alabama in 1992. (Ex. F, p. 1.) He

has held nine different professorships in immunology and pathology since 1996 all at Duke University

Medical Center. (Id.) He currently serves as Professor of Pathology, Associate Professor Immunology,

and Associate Professor of Medicine at Duke University Medical Center. (Id.) Dr. Staats is certified as a

medical technologist by the American Society of Clinical Pathologies. (Id. at 2.) He has served on the

editorial board of six different medical journals from 1996 to 2017, and as a peer reviewer for 18 different

journals since 1993. (Id. at 2-3.) Dr. Staats has served as primary or supporting author on 83 different

pieces of peer-reviewed medical literature covering various topics of pathology and immunology. (Id. at

21-25; Tr. 131.)

17 A significant portion of Dr. Staats’s initial report addresses Dr. Kinsbourne’s reliance on evidence

pertaining to the whole cell pertussis vaccination and his assertion regarding reversion of pertussis toxin;

however, because Dr. Kinsbourne effectively abandoned that reliance, it is not necessary to detail all of

the evidence submitted to rebut it. (Ex. E, pp. 4-8.) Nonetheless, I have reviewed and considered all of

the evidence pertaining to the whole cell pertussis vaccine that has been filed in this case.

21

Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909), 32 VACCINE 6847 (2014) (Ex. E,

Tab 11); Korsholm et al., supra, at Ex. E, Tab 7; Jean-Paul M. Valensi Julia R. Carlson,

& Gary A. Van Nest, Systemic Cytokine Profiles in BALB/c Mice Immunized with

Trivalent Influenza Vaccine Containing MF59 Oil Emulsion and Other Advanced

Adjuvants, 153 J. IMMUNOLOGY 4029 (1994) (Ex. E, Tab 1).)

Dr. Staats explains that, while Dr. Kinsbourne is correct to suggest that IL-1 is

released following vaccination and that IL-1 may play a role in development of epilepsy,

studies have shown that vaccinations do not necessarily induce elevated levels of IL-1β

in alum-adjuvanted vaccines such as DTaP. (Ex. E, p. 5 (citing Valensi, Carlson, & Van

Nest, supra, at Ex. E, Tab 1; Rachel Buglione-Corbett, Adjuvant-Specific Serum

Cytokine Profiles in the Context of a DNA Prime-Protein Boost HIV-1 Vaccine: A

Dissertation (April 29, 2013) (Ph.D dissertation, University of Massachusetts) (GSBS

Dissertations and Theses) (Ex. E, Tab 43)).) For example, vaccine-induced IL-1β has

been observed in mice that received HPV vaccines, such as Cervarix, which contains a

combination of alum and TLR4 ligand MPL adjuvants, and Gardasil, which contains only

alum adjuvants. (Id. at 6, (citing Tetsuo Nakayama, Yasuyo Kashiwagi, & Hisashi

Kawashima, Long-Term Regulation of Local Cytokine Production Following

Immunization in Mice, 62 MICROBIAL IMMUNOLOGY 124 (2018) (Ex. E, Tab 44)).)

However, intramuscular injection of Gardasil revealed no increase in IL-1β. (Id. (citing

Nakayama et al., supra, at Ex. E, Tab 44).) With regard to the effect on IL-1β induction

and subsequent seizures triggered by both whole cell and acellular pertussis vaccines,

studies demonstrate that the whole-cell pertussis vaccine has been associated with an

increase in IL-1β, fever, and convulsions, while acellular pertussis “neither increased IL-

1β nor induced behavioral changes in mice, but did induce the anti-inflammatory

cytokine IL-10.” (Id. (quoting Sheila Donnelly et al., Whole-Cell but Not Acellular

Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-

Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of

Vaccination, 69 INFECTION & IMMUNITY 4217 (2001) (Ex. Ex, Tab 19)).) Providing further

evidence against Dr. Kinsbourne’s contention that S.H.’s DTaP vaccine induced IL-1β

production that subsequently triggered her seizures, Dr. Staats cites his own study

which used recombinant IL-1 as a vaccine adjuvant in mice. Using a nasal vaccine,

which may provide direct access to the central nervous system, as well as intramuscular

vaccines, they did not find any link between the use of IL-1 as an adjuvant and the

induction of seizures. (Id. at 6-7 (citing William M. Gwinn et al., Effective Induction of

Protective Systemic Immunity with Nasally Administered Vaccines Adjuvanted with IL-1,

28 VACCINE 6901 (2010) (Ex. E, Tab 45).)

Dr. Staats also discusses the timing of S.H.’s seizures as it relates to Dr.

Kinsbourne’s theory. (Ex. E, p. 7-8.) He explains that seizure onset within one hour of

vaccination is not consistent with a vaccine-induced IL-1β triggered seizure. (Id. at 7.)

Studies have shown that induction of a fever due to IL-1 took at least two hours in

mouse studies and that the fever did not trigger any convulsion, thus it is unlikely that a

DTaP vaccine could induce a seizure in under one hour. (Id. (citing Gwinn et al., supra,

at Ex. E, Tab 45).) He further notes that, in clinical trials using infusion of recombinant

IL-1, fever was not observed until 2-6 hours after infusion, and there were no reported

22

seizures. (Id. (citing Daniel Weisdorf et al., Interluekin-1α Administered After

Autologous Transplantation: A Phase I/II Clinical Trial, 84 BLOOD 2044 (1994) (Ex. E,

Tab 51)).) Dr. Staats contends that the timing of IL-1 induced fevers suggests that the

timing of other IL-1 induced adverse events, such as seizures, would occur at the same

time or later, but not sooner, “since IL-1-induced fever can be induced by IL-1

stimulation of the [central nervous system].” (Id. (citing Anders Blomqvist & David

Engblom, Neural Mechanisms of Inflammation-Induced Fever, 24 NEUROSCIENTIST 381

(2018) (Ex. E, Tab 54)).) Finally, Dr. Staats explains that Dr. Kinsbourne relies on

sources, such as Dube et al. and subsequent commentary, which focus entirely on the

direct introduction of IL-1β to the brain, while vaccinations trigger cytokine responses in

the periphery, two cases which operate very differently from one another. (Id. at 8.)

ii. Dr. Staats’ supplemental report

Dr. Staats second report responds to specific comments made by Dr. Kinsbourne

in his final report. (Ex. H.) First, he addresses Dr. Kinsbourne’s revised opinion that

S.H.’s seizures could be triggered either by the DTaP vaccine, Prevnar 13 vaccine, or

both. (Id. at 1-2.) Dr. Staats explains that the Wise et al. study relied on by Dr.

Kinsbourne notes that seizures were observed alongside Prevnar 13 vaccination, but

the study was unable to identify anything beyond a temporal relationship and even

explicitly noted that many of the reported events may be unrelated to the vaccine. (Id.

(citing Wise et al., supra, at Ex. 53).)

Regarding Dr. Kinsbourne’s reliance on publications from the Vezzani group to

support his independent pathways theory, Dr. Staats points to one study, which stated,

“[i]t is notable that cells in the hippocampus, a region contributing to the origin and

spread of febrile seizures, synthesize IL-1β in response to fever or hyperthermia.

Remarkably, IL-1β is not synthesized or released during other types of experimental

seizures in the immature rodent . . . .” (Id. at 2 (quoting Vezzani & Baram, supra, at Ex.

22) (internal citations omitted).) Dr. Staats interprets this text to mean that the

hippocampus produces IL-1β in response to fever, which then induces febrile seizures.

(Id.) Further, the study indicates that IL-1β is not synthesized during other types of

seizures, suggesting that afebrile seizures are not caused by inflammation, and thus,

the study does not show that IL-1β can trigger afebrile seizures in the context of

vaccine-induced inflammation. (Id.)

iii. Testimony

During the hearing, Dr. Staats explained that the more rapid innate immune

response “takes some time to generate,” with cytokine production tending to peak 3-6,

and up to 12, hours after vaccination, while the adaptive immune response can take

upwards of a week or more. (Tr. 134-38.) Dr. Staats testified that the alleged

timeframe in this case (i.e. one hour or less) does not align with the general

understanding of vaccine-induced inflammatory cytokine responses. (Id. at 144.) He

explained that the earliest he has observed fever following vaccination where IL-1 was

used as an adjuvant was 2 hours, peaking at 2-6 hours, post-vaccination. (Id. at 136-

23

37.) Even after direct exposure with IL-1, fever was still not observed until 2 hours after

vaccination. (Id. at 137.) Dr. Staats suggested that the post-vaccination inflammatory

process may take longer where IL-1 is not directly administered. (Id. at 137-38.) Dr.

Staats testified that his expectation would be that vaccine-induced inflammation leading

to seizure would take at least two hours, or until after onset of fever, as fever is an

indicator of excessive systemic inflammation. (Id. at 140.) In fact, he indicated that

most of the literature he encountered on this topic of cytokine response to vaccination

involved fever as the adverse event. (Id. at 142.) He disclaimed the relevance of any

studies involving direct injection into the brain as this method allows for bypass of the

fever control center of the brain and entry into the seizure control portion of the brain.

(Id. at 141-42, 155.)

However, on cross-examination, Dr. Staats acknowledged that the studies he

relied upon to determine the reasonableness of the alleged timeframe did not measure

temperature at 20 minutes, 30 minutes, or 1 hour after vaccination. (Tr. 147, 149-50.)

He opined that the studies involving human trials provide stronger evidence as infusion

took place in the hospital where participants were continuously monitored. (Id. at 156.)

In response to the undersigned’s questioning, Dr. Staats clarified the relevance of some

of the studies cited in his own expert report. (Id. at 152-53.) He explained that vaccines

may induce an array of proinflammatory cytokines after vaccination, and the array may

not necessarily include IL-1. (Id. at 153-54.) Without measuring the cytokine response

in the particular individual, Dr. Staats could not say whether IL-1 was induced following

S.H.’s vaccinations, but studies examining IL-1β have generally shown it is not one of

the earlier cytokines to develop post-vaccination. (Id. at 154-55.)

V. Analysis

a. Diagnosis

The parties have offered conflicting opinions regarding whether the convulsive

events that S.H. experienced in May of 2015 were in fact seizures. Where the

existence and nature of the injury itself is in dispute, the Federal Circuit has concluded

that it is the duty of the special master “to first determine what injury, if any, [is]

supported by the evidence presented in the record before applying the Althen test to

determine causation.” Lombardi v. Sec’y of Health & Human Servs., 656 F.3d 1343,

1352-53 (Fed. Cir. 2001) (citing Broekelschen v. Sec’y of Health & Human Servs., 618

F.3d 1339 (Fed. Cir. 2010)).

At the hearing, Dr. Holmes suggested, on respondent’s behalf, that the events

that S.H. experienced in May of 2015 were actually “paroxysmal events,” which mimic

seizures but lack the postictal period that usually follows a generalized tonic-clonic

seizure. (Tr. 87-92; see also Ex. A, p. 11 (citing Obeid & Mikati, supra, at Ex. A, Tab

1).) Dr. Holmes indicated that many paroxysmal events “have only been recently

described or are only now being increasingly recognized.” (Ex. A, p. 11.) Obeid &

Mikati further recognize that diagnosis is challenging due to the limited repertoire of both

epileptic and nonepileptic paroxysmal clinical manifestations. (Obeid & Mikati, supra, at

24

Ex. A, Tab 1, p. 1.) Differentiating between nonepileptic and epileptic events mainly

relies on awareness of different mimickers of epilepsy and “the art of history-taking.”

(Id.) Dr. Holmes appeared to characterize paroxysmal events as a catch-all term. He

opined that “everything that shakes is not a seizure” and listed several different

conditions that involve convulsions without seizures, though he acknowledged he could

not identify a specific term that captures S.H.’s convulsions. (Tr. 88-89.) Dr. Holmes

further acknowledged it is difficult to distinguish seizures and paroxysmal events. (Id. at

89.)

Dr. Holmes noted that S.H.’s “lip-smacking” is not typical as the jaw generally

tenses and the mouth twitches during seizing, and that it is unusual for a child to cry out

after a seizure. (Tr. at 89-90.) Dr. Holmes further pointed to S.H.’s normal MRI, EEG,

and CT scan to bolster his evaluation of these events. (Id. at 91-92.) Though he

acknowledged that a normal EEG does not rule out the possibility of a seizure disorder,

Dr. Holmes opined that the absence of interictal abnormalities on both 24-hour EEGs

indicates a “pretty high” likelihood that S.H. was not experiencing active seizure

disorder. (Id. at 91.) However, during the hearing he qualified his opinion by stating, “I

cannot say, you know, [with] 100 percent confidence” that S.H. did not experience

seizures and noting in particular that “the mother’s story today was compelling for a

number of reasons for seizures.” (Tr. 87.) Further, Dr. Holmes agreed that, if the May

22 events were seizures, then the following May 26 and May 28 events were also likely

seizures. (Id. at 115-16.) He further agreed with Dr. Kinsbourne that, if the events were

considered seizures, then S.H. would meet the definition of “epilepsy” because she

would have had two or more unprovoked seizures. (Id. at 93.) In fact, when noting the

difficulty in distinguishing seizures and paroxysmal events, Dr. Holmes noted that S.H.’s

events “could well have been epileptic seizures.” (Tr. 89.)

I find the medical records preponderately establish that the events S.H.

experienced in May of 2015 were seizures. While respondent is correct in noting that

the medical records could be interpreted as expressing doubt as to whether petitioner

was experiencing active seizure disorder, S.H. was consistently assessed as

experiencing seizures, including assessments based on firsthand observation by the

treating physicians. (Ex. 6, p. 6 (Dr. Cha’s comment that S.H. presented with

“generalized seizures after receiving immunizations” on 5/22/2015); id. at 8-9 (ED

transfer note with recurrent seizures impression by Dr. Shook on 5/22/2015); id. at 20

(noting that Dr. Shook “witnessed seizure activity” on 5/22/2015); id. at 52-53 (ED

transfer note with seizure diagnosis by Dr. Tung on 5/26/2023); id. at 109-10 (ED

transfer note with recurrent seizure diagnosis by Dr. Tung on 5/28/2015); Ex. 4, pp. 10-

12 (assessment of seizure with provoking factor by Dr. Bose on 5/23/2015); id. at 13-14

(single seizure assessment by Dr. Marzo on 5/23/2015); id. at 83 (impression of

provoked seizures by Dr. Bose on 5/27/2015).) By May 27, 2015, S.H.’s treating

physicians were assessing her condition as epilepsy. (Ex. 4, 78 (assessment of

“absence epilepsy” by Dr. Fuqua on 5/27/2023); id. at 152-53 (epilepsy assessment by

Dr. Chinnici on 5/28/2015); id. at 157 (epilepsy assessment by Dr. Bose on 5/29/2015)).

In fact, Dr. Fuque was the sole treating physician that expressed some doubt,

commenting that her “spells . . . may or may not be seizures” because petitioner did not

25

report a postictal period. (Ex. 4, p. 79.) However, Dr. Fugue’s principal assessment

was absence epilepsy, which is not consistent with Dr. Holmes’s opinion regarding

nonepileptic paroxysmal events.18 (Id. at 78.) In the longer term, S.H.’s physicians

treated her with phenobarbital, an anti-seizure medication. (Id. at 154-61, 170-71.) Dr.

Holmes explained that he agreed with the decision to treat S.H. with phenobarbital

because Dr. Bose likely believed that the events were recurrent seizures based on

S.H.’s history and wanted to prevent further events. (Tr. 117, 120.)

Under the Vaccine Act, special masters must consider, but are not bound by,

“any diagnosis, conclusion [or] medical judgment . . . which is contained in the record

regarding the nature, causation, and aggravation of the petitioner’s illness, . . . injury,

[or] condition.” § 300aa-13(b)(1); see also Cucuras v. Sec’y of Health & Human Servs.,

993 F.2d 1525, 1528 (Fed. Cir. 1993) (recognizing that medical records generally

“warrant consideration as trustworthy evidence”). Special masters have “discretion to

determine the relative weight of evidence presented, including contemporaneous

medical records and oral testimony.” Caron ex rel. A.C. v. Sec’y of Health & Human

Servs., 136 Fed. Cl. 360, 376 (2018). In the instant case, the record reflects a

contemporaneous medical judgment that S.H.’s events were seizures. I have

considered Dr. Holmes’s additional opinion regarding paroxysmal events; however, it

contains at least some equivocation and does not outweigh the contemporaneous

medical judgments of the treating physicians. Even having reached a different

conclusion, Dr. Holmes was careful to note that he was not present for these events and

was not criticizing the treating physicians for deciding to treat these events as seizures.

Accordingly, I find that petitioner has preponderantly shown that S.H. suffered seizures

in May of 2015.

b. Severity Threshold

In order to state a claim for a vaccine-related injury under the Vaccine Act, a

vaccinee must have either:

(i) suffered the residual effects or complications of such illness, disability,

injury, or condition for more than 6 months after the administration of the

vaccine, or (ii) died from the administration of the vaccine, or (iii) suffered

such illness, disability, injury or condition from the vaccine which resulted

in inpatient hospitalization and surgical intervention.

§ 300aa-11(c)(1)(D).

Absence Epilepsy, DORLAND’S MEDICAL

18 Absence epilepsy is characterized by absence seizures.

DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=73435 (last visited Aug. 28,

2023). Absence seizures consist of sudden momentary breaks in consciousness of thought or activity and

are sometimes accompanied by clonic movements, especially in the eyelids. Absence Seizure,

DORLAND’S MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=105397

(last visited Aug. 28, 2023).

26

In this case, petitioner raised several separate allegations in her petition as to

why she has satisfied this requirement. First, she alleged that S.H. underwent a lumbar

puncture during her hospitalization that constitutes a surgical intervention. (ECF No. 1,

p. 4.) Second, she alleged that S.H. suffered a speech delay resulting from her

phenobarbital treatment that constitutes a residual effect or complication that persisted

for more than six months. (Id.) Third, she alleged that the need for an extended course

of phenobarbital itself constitutes a complication or residual effect of S.H.’s condition.

(Id.) By the time of her prehearing brief, petitioner had narrowed her argument to the

third of these contentions – that treatment with phenobarbital itself is sufficient to satisfy

the severity requirement. (ECF No. 81, pp. 22-23.) Because I agree with petitioner’s

narrower argument, it is not necessary to address the other contentions.

In Wright v. Secretary of Health & Human Services, the Federal Circuit

interpreted the Vaccine Act’s six-month severity provision to require a showing that the

“residual effects” of the vaccine injury were detrimental conditions, such as lingering or

recurring signs and symptoms of the vaccine injury. 22 F.4th 999, 1004-07 (Fed. Cir.

2022). As a result, the Federal Circuit held that B.W.’s testing for a possible recurrence

of thrombocytopenic purpura did not meet the Vaccine Act’s requirements because the

test revealed that there were no lingering symptoms or recurrence of the vaccine injury,

and there was no showing or argument that the testing was detrimental to B.W.’s health.

Id. at 1006. Additionally, B.W.’s “relatively non-invasive ongoing monitoring” itself did

not amount to an “ongoing disability” from his vaccine nor was it indicative that he

“suffered” or was “seriously injured” as there were no “lingering somatic effects at all

after six months.” Id. at 1007. Respondent argues that taking medication without any

apparent side effects, such as phenobarbital at issue in this case, is far less intrusive

and painful than even the testing and monitoring examined in Wright. (ECF No. 79, p.

18-19.)

However, citing two prior decision by special masters, the Wright court specified

that the decision did not disturb existing case law holding that a course of treatment

lasting longer than six months may be considered a “residual effect” within the meaning

of the Vaccine Act. 22 F.4th at 1007 (citing H.S. v. Sec’y of Health & Human Servs., No.

14-1057V, 2015 WL 1588366 (Fed. Cl. Spec. Mstr. Mar. 13, 2015); Faup v. Sec’y of

Health & Human Servs., No. 12-87V, 2015 WL 443802 (Fed. Cl. Spec. Mstr. Jan. 13,

2015)). The Federal Circuit explained,

During a long course of treatment, the patient generally has some lingering

condition such that symptoms will likely recur if the treatment were stopped.

Otherwise, the long course of treatment would not be necessary.

We do not decide today whether a course of testing or monitoring

that is part of the management or treatment of a condition, necessary even

in the absence of possible symptoms, could be a “residual effect.” In such

a case, the monitoring may be considered part of the treatment of a

condition that has not resolved, if the patient’s somatic condition increases

the risk of recurrence.

27

Id.

In H.S. v. Secretary of Health & Human Services, the special master found that

H.S. suffered the residual effects of a skull fracture for longer than six months, despite

only wearing a neck collar for about 12 weeks, because H.S.’s treating physicians

restricted his activity for an additional year, indicating a medical judgment that H.S.

remained in a vulnerable state and the injury had not fully resolved despite the lack of

outward symptoms. 2015 WL 1588366, at *2-3. In Faup v. Secretary of Health &

Humans Services, the experts agreed that A.F. was not exhibiting symptoms of juvenile

idiopathic arthritis for more than six months after vaccination at least in part because

she was medicated with Methotrexate to prevent the occurrence of those symptoms.

2015 WL 443802, at *4. While recognizing the necessity of Methotrexate to control

A.F.’s symptoms and prevent permanent joint damage, the experts explained that they

did not know whether such treatment “has anything to do with the achievement of

remission” but most doctors agreed that “judicious use of a medication like Methotrexate

is necessary simply because we do not know who, at disease onset, is earmarked to

follow a more or less favorable course.” Id. Accordingly, the special master found that

A.F.’s ongoing need for medication was a residual effect or complication of her vaccine

injury that lasted longer than six months. Id. Both H.S. and Faup stand for the

proposition, as stated by the special master in Faup, that “‘residual effects or

complications’ and ‘symptomatic’ are not synonymous; one can suffer from a disease

without exhibiting any clinical signs thereof.” Id.

Faup and H.S. contrast with a prior decision that noted that increased risk of

recurrence alone is insufficient to constitute a residual effect or complication within the

meaning of the Vaccine Act. Parsley v. Sec’y of Health & Human Servs., No. 08-718V,

2011 WL 2463539, at *5 (Fed. Cl. Spec. Mstr. May 27, 2011). Additionally, in a much

earlier case highlighted by respondent, a special master concluded, on facts very similar

to this case, that an extended course of phenobarbital did not constitute evidence of

complications or residual effects under the statute. Toebe v. Sec’y of Health & Human

Servs., No. 91-1623V, 1992 WL 101638 (Fed. Cl. Spec. Mstr. Apr. 23, 1992). The child

in Toebe experienced a series of afebrile seizures within hours of her DTaP vaccination,

requiring an extended course of phenobarbital that was maintained for approximately 28

months with consistently normal EEGs and without any further events. Id. at *1. The

Toebe petitioner argued that the course of phenobarbital and the treating physician’s

impression of seizure disorder was sufficient evidence to show that the child suffered

the residual effects or complications of the seizure disorder for more than six months.

Id. at *3. However, despite being placed on an extended course of phenobarbital and

experiencing some transient side effects from the medication and periodic testing, the

special master found that the child in Toebe had “no lasting measurable sequela,”

reasoning that a finding that phenobarbital blocked seizure activity would be speculative

without evidence of seizure activity after discontinuation of the medication. Id.

In this case, both parties’ experts explained that a child is not considered to have

achieved “remission” of epilepsy until after she has been successfully weaned from anti-

28

seizure medication such as phenobarbital. (Tr. 33, 122-23.) Up until that point, a child

who is on anti-seizure medication and not experiencing seizures is considered “under

seizure control” rather than in remission. (Id. at 122.) As Dr. Holmes explained, anti-

seizure medications, such as phenobarbital, “don’t cure epilepsy,” they only prevent

seizures from manifesting. (Id. at 120.) Thus, S.H. did not obtain her epilepsy

remission status until the phenobarbital was discontinued and she did not thereafter

have another seizure. This did not occur until more than six months post-vaccination.

While respondent is correct that “S.H. was unquestionably symptom-free within six

months of vaccination” (ECF No. 79, p. 18.), Dr. Holmes explained that it is impossible

to know whether there has been resolution of the seizure threshold or whether control of

the seizures is due to medication. (Tr. at 122.) Both parties’ experts testified to the

medical community’s general understanding that a child may remain on anti-seizure

medication for an extended period both due to the risk of recurrence and in order to give

the brain time to become less excitable. (Id. at 52-53, 117-20.) Dr. Holmes specifically

confirmed that brain excitability remains an ongoing condition even while administering

phenobarbital to prevent seizures. (Id. at 120-21.)

Respondent stresses a notation in the medical records indicating that S.H.’s

parents preferred to continue the phenobarbital until after S.H.’s 12-month

immunizations, stating that S.H.’s treating physicians “apparently did not require her to

take Phenobarbital for as long as she did.” (ECF No. 79, pp. 18-19 (citing Ex. 5, p.

228).) However, Dr. Holmes explained that the decision to discontinue anti-seizure

medication is not a rote decision but an assessment that is made on a case-by-case

basis and informed by specific clinical history. (Tr. 123-24.) Dr. Holmes thoroughly

explained that the decision to wean a child off medication is one that is made after a

“long discussion” with the parents about the pros and cons of discontinuing medication

in light of the fact that doctors do not know whether a patient is truly in remission until

after the medication is discontinued. (Id. at 123-24.) It is always a “tough question” due

to the lack of certainty. (Id.) When I asked Dr. Holmes if the decision to discontinue

phenobarbital is a case-specific clinical judgment, he answered, “[t]hat’s absolutely

correct.” (Id. at 124.) Even having cited factors that left S.H.’s own condition less

concerning, Dr. Holmes did not criticize the decision to keep S.H. on phenobarbital

through her 12-month vaccinations and wean her off the medications after those

vaccinations if there were no subsequent events. (Id. at 117-18.) He characterized it as

“proactive,” but did not suggest it was unreasonable or beyond normal clinical judgment.

In fact, he suggested the timing of S.H.s’ initial weaning was “appropriate” and a

“reasonable option here . . . waiting for time so the brain becomes less excitable.” (Id.

at 118, 120.)19

19

In any event, specifically asked at what point S.H.’s phenobarbital level would become subtherapeutic,

petitioner’s treating physician expected that it would take “up to 12 weeks for the phenobarbital level to

drop.” (Ex. 5, p. 307.) Therefore, even if S.H. had been weaned off her medication beginning at her

appointment on October 6, 2015, as originally recommended by her treating physicians, they would not

have considered her sub-therapeutic until December 29, 2015, which would also be six months after her

onset of May 22, 2015, when she had her first seizure. Arguably then, the prolonging of the

phenobarbital beyond the 12-month immunizations does not actually change the analysis.

29

In light of all of this, I conclude that this case is in line with Faup and H.S. given

that S.H.’s course of phenobarbital evidences a medical judgment based on S.H.’s own

clinical history that she “remained in a vulnerable state and had not returned to [her]

pre-vaccination condition of health” despite an absence of outward symptoms. H.S.,

2015 WL 1588366, at *3. Although Toebe reached a different conclusion on similar

facts, Toebe was resolved on a motion to dismiss without expert testimony regarding

the medical community’s understanding of the difference between seizure control and

remission or the considerations that go into determining when to conclude a given

patient’s anti-seizure treatment. 20 1992 WL 101638.

In light of all of the above, I find that petitioner has satisfied the six-month

severity requirement by virtue of S.H.’s extended course of phenobarbital.21

c. Althen Prong One

Under the first Althen prong, petitioner must provide preponderant evidence of a

medical theory causally connecting the subject vaccination with the alleged injury.

Althen v. Sec’y of Health & Human Servs., 418 F. 3d 1274, 1278 (Fed. Cir. 2005).

Petitioner’s theory must be “legally probable” but need not be “medically or scientifically

certain.” Knudsen ex rel. Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543,

548-49 (Fed. Cir. 1994). Moreover, petitioner is neither required to submit medical

literature or epidemiological studies nor to demonstrate a specific mechanism or a

generally accepted medical theory to meet her burden under Althen prong one. Morris

v. Sec’y of Health & Human Servs., No. 19-1750V, 2023 WL 5092691, at *6 (Fed. Cl.

Spec. Mstr. July 11, 2023) (citing Andreu v. Sec’y of Health & Human Servs., 569 F.3d

1367, 1378-79 (Fed. Cir. 2009)). However, petitioner’s theory “must be supported by a

sound and reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548 (citations

omitted).

It has been recognized in other cases that a vaccine can cause seizures in some

contexts, such as where a vaccinee has some genetic abnormality or where seizures

are febrile.22 For example, in this case respondent’s expert, Dr. Holmes, agrees that

20

Of course, rulings and decisions of other special masters are not binding. See Boatmon v. Sec’y of

Health & Human Servs., 941 F.3d 1351, 1358 (Fed. Cir. 2019). However, special masters are

encouraged to draw upon their accumulated experience assessing Vaccine Act claims when judging the

merits of individual claims. See Tenneson v. Sec’y of Health & Human Servs., 142 Fed. Cl. 329, 340

(2019); Hodges v. Sec’y of Health & Human Servs., 9 F.3d 958, 961 (Fed. Cir. 1993). As the Chief

Special Master has suggested, special masters would “be remiss in ignoring prior cases presenting

similar theories or factual circumstances, along with the reasoning employed in reaching such decisions.”

Simeone ex rel. R.S. v. Sec’y of Health & Human Servs., No. 20-1375V, 2023 WL 5286292, at *7 n.7

(Fed. Cl. Spec. Mstr. Feb. 24, 2023).

21 This conclusion is closely related to my conclusion that S.H. did suffer epilepsy as discussed in the

preceding section. If S.H. was not experiencing seizures, then this would raise additional questions with

respect to the role of phenobarbital in her treatment. (Tr. 126-29.)

22 See, e.g., Sharpe v. Sec’y of Health & Human Servs., No. 14-65V, 2021 WL 1291720, at *7-9 (Fed. Cl.

Spec. Mstr. Feb. 19, 2021) (concluding that the petitioner had sufficiently shown that the DTaP vaccine

30

vaccination can trigger febrile seizures. (Tr. 111.) However, Dr. Kinsbourne proposes

that two vaccinations, but principally the acellular pertussis-containing DTaP vaccine,

caused afebrile seizures without any established genetic susceptibility. (Ex. 7, p. 3.)

This represents a separate context in which numerous prior petitioners have not been

successful.23

Initially, Dr. Kinsbourne asserted that there is epidemiologic support for the idea

that vaccines can cause seizures, necessarily including afebrile seizures (Ex. 7, p. 3);

however, once pressed with respect to the DTaP vaccine, he later acknowledged that

caused-in-fact the significant aggravation of L.M.’s preexisting seizure disorder that was associated in

some part with an underlying genetic mutation); Ginn v. Sec’y of Health & Human Servs., No. 16-1466V,

2021 WL 1558342, at *5-7 (Fed. Cl. Spec. Mstr. Mar. 26, 2021) (concluding that vaccines can cause

febrile seizure that can in turn lead to epilepsy); Fuller ex rel. B.F., 2019 WL 7576382, at *14-16 (finding

that petitioner preponderantly established that the DTaP vaccine can cause complex febrile seizures);

see also Thompson v. Sec’y of Health & Human Servs., No. 15-671V, 2023 WL 21234, at *23-26 (Fed.

Cl. Spec. Mstr. Jan. 3, 2023) (concluding that petitioner had preponderantly shown that the Pentacel

vaccine, which includes DTaP, significantly aggravated an underlying and previously asymptomatic

Dravet syndrome). But see Osenbach v. Sec’y of Health & Human Servs., No. 16-419V, 2023 WL

5714809, at *25-26 (Fed. Cl. Spec. Mstr. Aug. 8, 2023) (distinguishing Sharpe and Ginn and citing

several cases where petitioners have been unsuccessful in proving causation where a child’s seizure was

presumably vaccine-induced but where the child was later determined to have Dravet syndrome), motion

for review filed (Fed. Cl. Sept. 7, 2023).

23 Borin ex rel. Borin v. Sec’y of Health & Human Servs., No. 99-491V, 2003 WL 21439673, at *11 (Fed.

Cl. Spec. Mstr. May 29, 2003) (finding that it is not plausible “that DPT would, in the absence of acute

encephalopathy and/or fever, cause brief seizures when the child is otherwise normal”); Nanez v. Sec’y of

Health & Human Servs., No. 20-1261V, 2003 WL 22434113, at *3-4 (Fed. Cl. Spec. Mstr. Sept. 23, 2003)

(concluding that petitioners had not presented a credible prima facie case showing that the acellular

pertussis vaccine caused their child’s afebrile seizures); K.L. v. Sec’y of Health & Human Servs., No. 12-

312V, 2017 WL 1713110, at *14-16 (Fed. Cl. Spec. Mstr. Mar. 17, 2017) (finding that petitioner had not

sufficiently shown that the HPV vaccine can cause afebrile seizures), aff’d, 134 Fed. Cl. 579 (2017);

Caredio ex rel. D.C. v. Sec’y of Health & Human Servs., No. 17-0079V, 2021 WL 4100294, at *30-34

(Fed. Cl. Spec. Mstr. July 30, 2021) (rejecting petitioner’s medical theory that a molecular-mimicry driven

cross-reaction instigated by the flu vaccine caused afebrile seizures, eventually evolving into an

autoimmune form of epilepsy or epilespia partializ continua), aff’d, 2021 WL 6058835 (Fed. Cl. Dec. 3,

2021); Chavez v. Sec’y of Health & Human Servs., No. 16-1479V, 2022 WL 3368502, at *23-25 (Fed. Cl.

Spec. Mstr. July 19, 2022) (finding petitioner’s medical theory, which proposed that adjuvants in the

Pediarix, pneumococcal conjugate, haemophilus influenzae type B, and rotavirus vaccines provoked the

production of proinflammatory cytokines and caused afebrile seizures, was not sound and reliable); Gram

ex rel. A.L.M. v. Sec’y of Health & Human Servs., No. 15-515V, 2022 WL 17687972, at *41-47 (Fed. Cl.

Spec. Mstr. Nov. 16, 2022) (finding as unpersuasive petitioner’s theory that an IL-1β mediated response

to MMR vaccination can trigger afebrile seizures and explaining that “there is no convincing evidence that

vaccine can cause seizures in the absence of a fever”); Walters v. Sec’y of Health & Human Servs., No.

15-1380V, 2023 WL 3750716, at *32 (Fed. Cl. Spec. Mstr. June 1, 2023) (concluding that petitioner had

not provided preponderant evidence showing that the DTaP vaccine can cause, in pertinent part, afebrile

seizure activity), aff’d, 2023 WL 5274006 (Fed. Cl. July 31, 2023), appeal docketed, No. 23-2369 (Fed.

Cir. Sept. 8, 2023); Hargrove ex rel. A.F.M. v. Sec’y of Health & Human Servs., No. 17-233V, 2023 WL

8071917, at *33-36 (Fed. Cl. Spec. Mstr. Oct. 27, 2023) (finding that petitioner had not proven that

afebrile seizures can be caused by DTaP vaccination through a cytokine driven process); Bechel v. Sec’y

of Health & Human Servs., No. 16-887V, 2023 WL 8588184 (Fed. Cl. Spec. Mstr. May 22, 2023)

(determining that petitioners did not carry their burden of showing that the MMR or DTaP vaccines can

cause afebrile seizures), aff’d (Fed. Cl. Nov. 20, 2023).

31

he could not locate any epidemiologic evidence that compared incidences of afebrile

seizures following DTaP vaccinations against background rates or controls and that he

ultimately is “not in a position to rely on epidemiological evidence on this issue.”24 (Ex.

28, p. 4). He later attempted to reverse course, adding assertions with respect to the

Prevnar 13 vaccine and suggesting during the hearing that there is “some

epidemiological backing” for his theory. (Tr. 35-36.) However, the additional literature

he cited again centers on an association between febrile seizures and vaccination. (Id.

35-37 (citing Sun et al., supra, at Ex. 21).) Importantly, and contrary to Dr.

Kinsbourne’s competing opinion, Dr. Holmes explained that in febrile seizures the fever

itself causes the seizure. (Id. at 106-07, 111-13.) Given the accepted connection

between fever and seizure on the one hand, and vaccination and fever on the other, Dr.

Kinsbourne has not shown that it would be reasonable to rely on statistical findings that

include post-vaccination febrile seizure as evidence that the subject vaccines can cause

seizures in the absence of a seizure-causing fever. Rather, he acknowledged in his

testimony that vaccine-induced afebrile seizures are rare enough to go undetected in

epidemiological studies.25 (Id. at 35-36.)

Dr. Kinsbourne alternatively sought to rely on literature pertaining to afebrile

seizures in those with Dravet syndrome. (Ex. 28, pp. 4-6 (citing Francesca Ragona et

al., Dravet Syndrome: Early Clinical Manifestations and Cognitive Outcome in 37 Italian

Patients, 32 BRAIN & DEV. 71 (2010) (Ex. 39); Berg et al., supra, at Ex. 29; Ingrid E.

Scheffer, Commentary, Vaccination Triggers, Rather Than Causes, Seizures, 15

EPILEPSY CURRENTS 335 (2015) (Ex. 40); Fernando Cendes & Raman Sankar,

Vaccinations and Febrile Seizures, 52 EPILEPSIA 23 (2011) (Ex. 31)).) However, he

likewise failed to substantiate how epidemiology concerning afebrile seizures following

24 In his initial report, Dr. Kinsbourne additionally opined that the toxoided pertussis toxin in the acellular

pertussis vaccine can spontaneously revert to toxin, causing similar consequences as the older

formulations of the whole cell pertussis vaccine. (Ex. 7, p. 3.) However, Dr. Kinsbourne could not

substantiate this theory. As pointed out by Dr. Staats, the two manuscripts that Dr. Kinsbourne provided

in support of his spontaneous reversion theory simply discuss safety measures, e.g., ensuring that the

toxoided pertussis does not revert to active pertussis, taken by vaccine producers before regulatory

approval of the vaccines. (Ex. E, p. 4.) I have previously discussed the many cases that persuasively

explain why studies relating to the safety of the whole cell pertussis vaccine are not applicable to the

acellular pertussis vaccine. See, e.g., Kottenstette, 2020 WL 4197301, at *8-10; Bangerter ex rel. D.B.,

2022 WL 439535, at *22-23. Dr. Kinsbourne ultimately disavowed his spontaneous reversion theory,

stating that he was unable to locate any further literature in support of his theory. (Tr. 65.) He thus

abandoned his intimation that any propensity of the whole cell pertussis vaccine to cause seizures should

inform interpretation of epidemiology relating to the acellular pertussis vaccine.

25 I do acknowledge that, per Dr. Kinsbourne’s opinion, fever is a concomitant rather than necessarily

causal feature of febrile seizures. (Ex. 28, pp. 1-2.) Accordingly, one could argue that under Dr.

Kinsbourne’s rationale the epidemiologic data should be interpreted without distinguishing between febrile

and afebrile seizures. For all the reasons discussed herein, however, I am not persuaded by Dr.

Kinsbourne’s theory. In any event, even if Dr. Kinsbourne’s theory that there are multiple pathways for

cytokines to cause seizures were persuasive, this would not automatically refute that fevers themselves

can cause seizures in at least some cases, as Dr. Holmes has opined. Accordingly, the inclusion of

febrile seizures in the data would still complicate Kinsbourne’s reliance on that data with respect to

afebrile seizures. Ultimately, while noting these points in the interest of completeness, it is up to

petitioner and Dr. Kinsbourne to establish the relevance of the epidemiology they would seek to rely upon

and they have not done so.

32

vaccination of children with Dravet syndrome, a condition of which S.H. does not suffer,

is analogous to this case, especially where his premise that S.H. had a low seizure

threshold represents conjecture unsupported by record evidence. (Tr. 42-44, 62.) As

Dr. Holmes explained, Dravet syndrome is a condition in which a sodium channel

mutation results in epilepsy. (Id. at 95.) Even if a vaccine causes a seizure in a Dravet

syndrome patient, the vaccine did not cause the epilepsy, the Dravet syndrome did.

(Id.) And even in that context, where there may be many things that can provoke a

seizure in a predisposed individual, temperature still appears to be the primary culprit in

seizure activity. (Id. at 111.) By contrast, Dr. Kinsbourne acknowledged during the

hearing that he has no basis to explain why S.H. purportedly had an unusually low

seizure threshold at the time of seizure onset; he simply concludes that she did “for

whatever reason – we don’t know.” (Id. at 43; but see id. at 96 (Dr. Holmes opining S.H.

did not have a lowered seizure threshold).) In any event, Dr. Kinsbourne’s suggestion

that findings relative to Dravet syndrome can be meaningfully applied outside of the

context of that very specific vulnerability is Dr. Kinsbourne’s conjecture alone. (Id. at 97

(Dr. Holmes refuting Dr. Kinsbourne’s reliance on Dravet syndrome literature).)

Of course, petitioner need not present epidemiologic studies to meet her burden

of proof under Althen prong one. Andreu, 569 F.3d at 1378. In that regard, Dr.

Kinsbourne also presented a separate theory of causation. Dr. Kinsbourne explains

that vaccination causes the release of proinflammatory cytokines, including IL-1β. (Ex.

7, p. 3 (citing Chen, Howard, & Oppenheim, supra, at Ex. 10)).) He further observes

that IL-1β in turn can cause or contribute to fever while also having a “well-documented

propensity to cause seizures.” (Id. (citing Vezzani & Baram, supra, at Ex. 22; Sanon,

Desgent, Carmant, supra, at Ex. 19).) Dr. Kinsbourne indicates that the presence of

fever is not required for IL-1β to lead to seizures. (Ex. 28, p. 2 (citing Dube et al., supra,

at Ex. 48; Mazarati et al., supra, at Ex. 33; Vezzani & Baram, supra, at Ex. 22).) In

particular, he stresses that a study by Dube et al. found that high doses of IL-1β can

provoke seizures “without increased brain temperature.” (Id. (quoting Dube et al.,

supra, at Ex. 48, pp. 3-4).) Dr. Kinsbourne thus contends that IL-1β has been shown to

induce seizures by a pathway independent of the pathway by which a release of

cytokines can cause fever. (Ex. 45, p. 4.) Specifically, Dr. Kinsbourne submits that “the

flow of cytokines to the hypothalamic control center for temperature and the flow of

cytokines to the hippocampal and neocortical seizure generators are independent of

each other.” (Id.; see also Tr. 39.) There is no dispute that the papers cited by Dr.

Kinsbourne hypothesize multiple pathways by which IL-1β could cause seizures (Tr.

157 (Dr. Staats acknowledging that the Dube articles “proposes” two different

pathways)); however, respondent’s experts raise several points that diminish the value

of this hypothesis.

Dr. Holmes cautions that it is unlikely that cytokines produced peripherally by

vaccination would be able to traffic across the blood brain barrier without also producing

other consequences, such as fever. (Tr. 101, 112-13; Ex. D, pp. 1-2.) Even Dr.

Kinsbourne’s own use of the term “concomitant” to describe his understanding of the

relationship between fevers and seizures implies as much, even as he urges that the

two events manifest by independent pathways. (Ex. 45, p. 5.) Although Dr. Holmes

33

agrees that cytokines can produce endogenous fever, he indicates that the relevant

literature establishes that the increase in cytokines associated with seizures is a

response to the seizure, not its cause. (Ex. D, pp. 1-2 (citing Li et al., supra, at Ex. D,

Tab 7).) For example, Dr. Holmes cites a review paper that looks at some of the same

research as cited by Dr. Kinsbourne, as well as a broader review of studies, both human

and animal, that examine the role of cytokines in epilepsies. (Li et al. supra, at Ex. D.)

Reviewing IL-1β, the authors explain that while animal models have supported the

epileptic potential of IL-1β only at high doses, at least some human studies have had

more mixed results, citing two studies that failed to detect elevated IL-1β following

generalized tonic-clonic seizures, such as those at issue in this case. (Id. at p. 2.)

Thus, consistent with Dr. Holmes’s view, the authors indicate that while an association

between IL-1β and seizures may exist, a distinct role of IL-1β in epilepsy has not been

shown. (Id.)

Dr. Staats further explained that in the studies cited by Dr. Kinsbourne “the route

of delivery is somewhat artificial when compared to vaccine-induced cytokine

production.” (Tr. 141.) For instance, Dr. Staats notes that the Dube study did not utilize

vaccination nor demonstrate how cytokine-induced inflammation can cause seizure

without fever. (Ex. H, p. 3.) Moreover, Dr. Staats opines that the Dube study is too far

removed from the real-world context of vaccine-induced innate immune response to be

informative. (Tr. 141-42; Ex. H, p. 3.) Both of respondent’s experts stress that IL-1β

was directly injected into the brains of the mice at a much higher dosage than would be

expected following vaccination. (Tr. 141, 155; Ex. H, p. 3; Ex. E, p. 8; see also Ex. D, p.

2 (Dr. Holmes notes that the dosages were “1000X greater than those found in blood

following vaccination in humans”).) Ultimately, Dr. Kinsbourne agreed during the

hearing that the Dube study involved higher levels of IL-1β than would be expected in a

real world context.26 (Tr. 61-62.)

Instead, Dr. Staats cites other studies contextualizing the degree to which IL-1β

circulates in the blood after vaccination. Specifically, in a human trial where interleukin-1

alpha (“IL-1α”) 27 was delivered intravenously over 6 hours at much higher doses than

normally induced by peripheral activation of the innate immune system, fever developed

at 2-6 hours of infusion and there were no reports of seizure activity. (Ex. E, p. 7 (citing

Weisdorf et al., supra, at Ex. E, Tab 51).) In another human trial where IL-1α was

26 Dr. Staats also offers competing animal studies that he suggests further undermine Dr. Kinsbourne’s

independent pathways theory. (Ex. H, pp. 2-3; Ex. E, pp. 4-8.) For example, he cites a mouse model that

compared the effect of parenteral administration of the whole cell pertussis vaccine and acellular

pertussis vaccination on IL-1β levels and seizure-like behavioral changes, finding that immunization with

the acellular pertussis vaccine induced neither an elevation of IL-1β in the brain nor behavioral changes.

(Ex. E, p. 6 (citing Donnelly et al., supra, at Ex. E, Tab 19).)

27 Dr. Staats explained that IL-1α and IL-1β are forms of IL-1 that bind to the same receptors and have

similar biological activity. (Tr. 138-39; Exs. E, p. 5; John W. Smith, et al., The Effects of Treatment with

Interleukin-1α on Platelet Recovery After High-Dose Carboplatin, 328 NEW ENG. 756, 759 (Ex. E, Tab 53,

p. 4).) Accordingly, studies concerning IL-1α are relevant at least to the extent that they concern the

outcome of stimulation with IL-α and IL-1β. (Tr. 139.) In his work, Dr. Staats uses a recombinant IL-1

that is produced in a laboratory as a purified protein. (Id. at 138-39.)

34

administered by intravenous infusion for 5 days, several adverse effects were observed,

including fever, but there was no mention of seizure. (Id. (citing John W. Smith, The

Effects of Treatment with Interleukin-1α on Platelet Recovery After High-Dose

Carboplatin, 328 NEW ENG. J. MED. 756 (1993) (Ex. E, Tab 53)).) In his own work, Dr.

Staats has found that, even with direct application of IL-1 at concentrations not likely to

be induced by vaccines and by routes that may allow IL-1 easier access to the central

nervous system, there was no link between the use of IL-1 as a vaccine adjuvant and

the induction of seizures. (Id. at 6-7.)

In any event, the specific purpose of the Dube study relied on heavily by Dr.

Kinsbourne was to test “the hypothesis that endogenous IL-1β contributes to the

mechanisms of fever-induced seizures, and that these IL-1β actions are independent of

genetic background.” (Dube et al., supra, at Ex. 48, p. 3 (emphasis added).) In that

regard, the finding relied upon by Dr. Kinsbourne – that high doses of IL-1β could

produce seizures without increased brain temperature – was not reported in isolation. It

was one of three principle findings, along with findings relating to IL-1β signaling in the

context of febrile seizures, that led the authors to “implicate IL-1β among the

mechanisms by which fever provokes seizures in the developing brain.” (Id. at 5.) Dr.

Staats explains that Dube et al. used a model of direct injection of IL-1β into the brain

that actually bypassed the fever control center of the brain, making it impossible to

conclude that the study demonstrates that IL-1 can actually induce a seizure in the

absence of fever. (Tr. 155.) Similarly, Vezzani & Baram indicated: “The mechanisms

by which fever evokes febrile seizures are not fully elucidated, but a role for IL-1β is

supported by several lines of evidence.” (Vezzani & Baram, supra, at Ex. 22, p. 4.)

However, the authors also observed that IL-1β “is not synthesized or released during

other types of experimental seizures in the immature rodent.” (Id.) On respondent’s

behalf, Dr. Staats interprets this observation as implying that afebrile seizures are not

caused by inflammation as would be seen with febrile seizures following vaccination.

(Ex. H, p. 2.)

Finally, even if Dr. Kinsbourne succeeded in demonstrating a theory by which

S.H.’s first seizure could be considered vaccine-caused, he would still need to

demonstrate that the first seizure resulted in epilepsy. In that regard, Dr. Holmes is also

persuasive in rebutting Dr. Kinsbourne’s theory that brief afebrile seizures of the type

suffered by S.H. beget further seizures. (Tr. 97-100.) Where Dr. Kinsbourne has in the

past been successful in presenting his theory that seizures beget seizures, the initiating

seizures were complex febrile seizures.28 See, e.g., Fuller, 2019 WL 7576382, at *15-

16. Here, however, there is no debate that S.H.’s seizures only lasted around 2-3

28 As previously noted, rulings and decisions of other special masters are not binding. See supra note 21.

Here, I note Fuller only to acknowledge the context in which Dr. Kinsbourne’s theory has been otherwise

accepted and to elucidate why the instant case presents a different scenario. In response to my inquiry

into whether his prior cytokine-based theory in Fuller conflicts with his proposed theory in this case, Dr.

Kinsbourne explained that his report in Fuller cited medical literature that was relevant to that case but

that did not “tell the whole story.” (Ex. 28, pp. 3-4.) He then clarified his separate pathway theory, which I

have already explained is unpersuasive on this record. (Id.) However, the actual question presented in

Fuller (i.e., whether complex febrile seizures can lead to epilepsy) is not before me.

35

minutes. There is similarly no question that the events were not febrile.29 Dr.

Kinsbourne ultimately conceded in his testimony that S.H. suffered brief, generalized

tonic-clonic seizures, despite previously opining in his expert report that she suffered

complex seizures with focal features. (Compare Tr. 33, with Ex. 28, p.3.) Dr. Holmes

likewise testified that, if seizures, S.H.’s events were more likely generalized tonic-clonic

seizures than complex seizures. (Tr. 115.) In that context, though there is no dispute

that seizures themselves produce some inflammation, Dr. Holmes explained that Dr.

Kinsbourne’s theory is a “huge stretch” of the cytokine literature (which itself does not

involve vaccination) and not plausible. (Id. at 100, 103-04.)

Dr. Holmes explained that Dr. Kinsbourne’s theory is a misapplication of the so

called “kindling theory,” which is itself no longer viewed favorably by the medical

community. (Tr. 98-99.) While seizure activity can cause the brain to become more

susceptible to seizures, it does not cause epilepsy resulting in spontaneous afebrile

seizures. (Id.) According to Dr. Holmes, although epileptic seizures are related in the

sense that they are all due to the same underlying cause, it is not the case that seizure

A causes seizure B, etc. (Id. at 124-25.) He flatly denied that a three-minute seizure

like those present in this case would produce a cytokine response that would explain

any subsequent seizure, even one occurring shortly after the first event. (Id. at 99-100.)

Even in the more serious condition of status epilepticus, which S.H. is “not even close to

having,” studies have shown anti-inflammatory treatments have not worked, casting

doubt on any relationship to inflammation. (Id. at 99.)

For these reasons, I find that petitioner has not satisfied Althen prong one.

d. Althen Prong Two

The second Althen prong requires that petitioner demonstrate a logical sequence

of cause and effect, which is usually supported by facts derived from petitioner’s

medical records. Althen, 418 F.3d at 1278; Andreu, 569 F.3d at 1375-77; Capizzano v.

Sec’y of Health & Human Servs., 440 F.3d 1317, 1326-27 (Fed. Cir. 2006); Grant, 956

F.2d at 1148-49. The opinions and views of petitioner’s treating physicians are entitled

to some weight as treating physicians are in the best position to determine whether the

subject vaccine was the reason for the alleged injury. See § 300aa-13(b); Capizzano,

440 F.3d at 1326. However, medical records and/or statements of treating physicians

do not per se bind the special master to adopt such conclusions, even if they must be

considered and carefully evaluated. See § 300aa-13(b)(1) (“Any . . . diagnosis,

conclusion, judgment, test result, report, or summary shall not be binding on the special

master . . . .”); Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 745 n.67

(explaining that nothing “mandates that the testimony of a treating physician is

sacrosanct—that is much be accepted in its entirety and cannot be rebutted”).

29 There was some suggestion in Dr. Kinsbourne’s expert reports that S.H. could have had a fever that

was either inhibited by a release of IL-1β or had gone undetected by her treating physicians because it

was not a significant increase in temperature. (Exs. 28, p. 5 (“If fever is in evidence, it is very low

grade.”); Ex. 45, p. 4 (“A brief low-grade fever could easily be overlooked.”).) At the hearing, Dr.

Kinsbourne clarified that there was no documented fever preceding S.H.’s seizures. (Tr. 45, 60-61.) As

such, any suggestion that S.H. may have had a low-grade fever is not supported by the record.

36

There is some indication in the records that S.H.’s treating physicians were

willing to attribute S.H.’s initial seizure event to her preceding vaccinations. (Ex. 4, pp.

10, 12, 14.) However, while one of S.H.’s treating physicians, Dr. Marzo, reported the

initial event to VAERS (Ex. 4, p. 14), S.H.’s neurologist, Dr. Sarco, specifically noted

that the absence of fever was more concerning for epilepsy (Ex. 27, p. 71). Moreover,

both of S.H.’s neurologists – Dr. Bose and Dr. Sarco – expressed doubt that the

vaccine(s) caused S.H.’s seizures once they recurred. (Ex. 5, pp. 2-3, 42-43, 71-72,

229.) Accordingly, even crediting Dr. Marzo’s VAERS report as some evidence

pertaining to the cause of S.H.’s initial seizure, the treating physician opinions on the

whole still do not meaningfully support Dr. Kinsbourne’s opinion. Whereas Dr.

Kinsbourne is explicit in opining that S.H.’s vaccinations caused not merely a single

seizure event, but her epilepsy (see Ex. 24), Dr. Sarco in particular considered

“immunization induced events” and “inherent mild epilepsy” to be alternative

explanations. (Ex. 27, p. 71).

Respondent’s experts also challenge the idea that Dr. Kinsbourne’s theory could

be operative in the context of S.H.’s own clinical history. Specifically, Dr. Holmes

contends that, if Dr. Kinsbourne’s theory were correct, then there would have to be

some evidence of an ongoing cytokine-induced inflammatory process, such as a fever

or some indication of inflammation in the MRI, EEG, spinal fluid examination, or clinical

history. (Tr. 100-01; Ex. G, p. 2.) Dr. Staats suggested that, even if fever serves only

as a proxy for detecting excessive inflammation, it would be impossible to posit

excessive post-vaccination inflammation leading to seizure in the absence of such a

proxy. (Tr. 138.) Dr. Kinsbourne’s only response is to contend that S.H.’s presentation

is explained by a low seizure threshold that resulted in rapid seizure onset, which in turn

resulted in insufficient time for a clinically measurable fever to develop. (Ex. 45, p. 5-6.)

Yet, Dr. Kinsbourne acknowledged that genetic testing confirmed that S.H. did not have

any predisposition to seizures or epilepsy (Tr. 62) and he conceded having no basis for

asserting that S.H. had any unusually low seizure threshold in the first place (Id. at 43-

44). That is, Dr. Kinsbourne seeks to support his explanation of events by reference to

a vulnerability – an unusually lowered seizure threshold – that he cannot substantiate

based on any facts within S.H.’s own medical history.30 In fact, when pressed during

the hearing, Dr. Kinsbourne could not distinguish S.H.’s medical course from the typical

course of childhood epilepsy, apart from what he indicates as coincident timing of

vaccination. (Id. at 75.) Dr. Holmes explained that epilepsy is “pretty common” in

children. (Id. at 94.) It is more common in children than adults, affecting up to about

1% of children. (Id.)

30 Notably, Dr. Kinsbourne has been repeatedly criticized for employing circular logic when the facts fail to

align with his theory. See, e.g., Holmes v. Sec’y of Health & Human Servs., No. 08-185V, 2011 WL

2600612, at *14 (Fed Cl. Spec. Mstr. Apr. 26, 2011) (observing that “[t]o rely on the initial seizures

themselves as evidence of a lowered seizure threshold would be circular reasoning” and rejecting Dr.

Kinsbourne’s opinion for seeking to rely on facts not supported by the medical records); Dodd v. Sec’y of

Health & Human Servs., No. 09-0585V, 2013 WL 3233210, at *14 (Fed. Cl. Spec. Mstr. June 5, 2023)

(explaining that “Dr. Kinsbourne’s circular logic, that one event was caused by another simply because

the second event occurred, is also unavailing”), review denied, 114 Fed. Cl. 43 (2013); Gram ex rel.

A.L.M., 2022 WL 17687972, at *46 (same).

37

Instead, Dr. Kinsbourne’s opinion is based on his belief that there could be no

other “feasible alternative cause” because so little time had passed between vaccination

and onset of seizure activity. (Tr. 46-48.) But the Federal Circuit has explained that,

“[a]lthough probative, neither a mere showing of a proximate temporal relationship

between vaccination and injury, nor a simplistic elimination of other potential causes of

the injury suffices, without more, to meet the burden of showing actual causation.”

Althen, 418 F.3d at 1278 (citing Grant, 956 F.2d at 1149). That is, vaccines are not the

cause of every unfortunate event that occurs soon after their administration. See

Pafford v. Sec’y of Health & Human Servs., No. 01-0165V, 2004 WL 1717359, at *9

(Fed. Cl. Spec. Mstr. July 16, 2004), aff’d, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d 1352

(Fed. Cir. 2006), cert. denied, 551 U.S. 1102 (2007). Here, I am not persuaded by Dr.

Kinsbourne’s mere post hoc, ergo propter hoc reasoning. In fact, for the reasons

discussed under Althen prong three, the timing of S.H.’s seizures relative to vaccination

more likely counsels against implicating S.H.’s vaccinations.

For these reasons, I find that petitioner has not satisfied Althen prong two.

e. Althen Prong Three

The third Althen prong requires “a showing of a proximate temporal relationship,”

or “medically-acceptable temporal relationship,” between the vaccination and alleged

injury. Althen, 418 F.3d at 1278, 1281. Petitioner must provide “preponderant proof

that the onset of symptoms occurred within a timeframe for which, given the medical

understanding of the disorder’s etiology, it is medically acceptable to infer causation-in-

fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically acceptable

timeframe must coincide with Althen prong one, that is, with the theory of how the

subject vaccine can cause the alleged injury. Id.; Shapiro v. Sec’y of Health & Human

Servs., 105 Fed. Cl. 353, 360 (2012) (explaining that petitioner must first establish a

medically acceptable timeframe to infer causation, i.e., a medically acceptable

timeframe in which symptoms would be expected to arise if the alleged injury was

caused by the subject vaccine, and then, petitioner must show that the onset of the

alleged injury occurred during that timeframe), aff’d, 503 Fed. App’x 952 (Fed. Cir.

2013); Williams v. Sec’y of Health & Human Servs., No. 17-255, 2023 WL 4401095, at

*23 (Fed. Cl. Spec. Mstr. June 12, 2023).

The medical records reflect that S.H. was administered the vaccinations at issue

in this case at about 9:50AM on May 22, 2015. (Ex. 3, p. 110.) When she first

presented for care for her reported seizures, her parents reported the vaccines had

been administered at about 9:30AM. (Ex. 6, p. 3.) The seizure occurred at about

10:30AM that same morning, at which time S.H. was taken directly to the emergency

department. (Id.) She was first triaged at the emergency department at 11:10AM. (Id.

at 10.) Accordingly, S.H.’s first seizure occurred an hour or less after her vaccination.

Petitioner asserts that onset of S.H.’s afebrile seizures approximately one-hour post-

vaccination is medically acceptable. (ECF. 81, pp. 20-21.) However, Dr. Kinsbourne

provided no medical explanation to support that assertion. Based on epidemiology, he

38

opined that the risk window for post-vaccination seizures is generally considered to be

within the first 24-72 hours, going so far as to say that it is “most often within a matter of

hours,” but he explained that the available epidemiology does not break down data hour

by hour. (Tr. 48; Ex. 7, p. 4.) Accordingly, epidemiology does not answer this

question.31

In contrast, Dr. Staats presented an opinion supported to at least some degree

by medical literature that onset in this case was too rapid to be attributed to the vaccine

based on the specifics of the theory Dr. Kinsbourne has proposed. (Ex. E, p. 7.)

Specifically, Dr. Staats explained that post-vaccination cytokines generally peak 3 to 12

hours after vaccination. (Tr. 134.) Even in experimental animal models administering

high doses of adjuvant, the first fevers manifest after two hours and measurable

cytokines begin at about three hours. (Id. at 136-37.) Thus, Dr. Staats opines that

vaccine-induced inflammation at the one-hour mark would not be robust enough to

cause a seizure event, especially in the absence of fever. (Id. at 140.) Dr. Staats

stressed that the two-hour post-vaccination events in experimental studies stem from an

artificial direct administration of IL-1 whereas, in a true clinical setting, a seizure would

be a downstream consequence of proinflammatory cytokines reaching the brain,

meaning that a one-hour onset is simply not compatible with a cytokine response

leading to an adverse event. (Id. at 144.)

Petitioner’s counsel’s cross examination raised an important limitation regarding

several of the studies cited by Dr. Staats – namely, that they did not actually measure

fever or cytokine response within one hour of inducing the response. (Tr. 146-50

(discussing Gwinn et al., supra, at Ex. E, Tab 45; Emmanuel Katsanis et al., Infusions of

Interleukin-1α After Autologous Transplantation for Hodgkin’s Disease and Non-

31 Dr. Kinsbourne cites several pieces of medical literature that provide some support for his claim that

onset of post-vaccination seizures can be between 24 and 72 hours after vaccination. (Ex. 7, p. 2, 4)

(citing von Spiczak et al, supra, at Ex. 20; Sun et al., supra, at Ex. 21).) However, Dr. Holmes points out

that the sole piece of medical literature that Dr. Kinsbourne provides to support his assertion that post-

vaccination seizures can occur within less than 24 hours is not applicable in this case given that the study

examined whole cell pertussis vaccination. (Ex. A, p. 13; Tr. 97 (discussing Murphy, Sarff, & Marquardt,

supra, at Ex. 18.)) While Murphy et al. observed a minimum one-hour interval between immunization with

the whole cell pertussis vaccine and onset of seizure activity among 22 subjects, the study had very

significant limitations. First, the study was based on questionnaires sent to parents. There is no

indication that the reported onset periods were confirmed in any way. Second, the authors stressed that

the questionnaires were not sent to a random sample of families with vaccinated children. Instead, the

authors sought out parents that already believed their child had suffered an adverse reaction. Third, no

control group was utilized. Thus, the authors explain “[c]are must be taken to avoid overinterpretation of

our data. There are inherent biases secondary to the method of collection . . . The long delay from the

initial seizure to the report in many subjects, while permitting prolonged follow-up, did limit the accuracy of

some of the collected data. The lack of control subjects make it difficult to ascribe a causal relationship to

pertussis vaccine.” (Murphy, Sarff, & Marquardt, supra, at Ex. 18, p. 4.) Moreover, the study’s discussion

is inadequate to characterize the specific subject that represented the minimum one-hour latency.

Among the 22 study subjects, one was already ill with suspected whooping cough at the time of

vaccination, one had tuberous sclerosis believed to explain the seizures, and two were siblings

suspicious for a familial predisposition. Two of the subjects ultimately suffered infantile spasms.

39

Hodgkin’s Lymphoma Induce Effector Cells with Antilymphoma Cytolytic Activity, 14 J.

CLINICAL IMMUNOLOGY 205 (1994) (Ex. E, Tab 52); Smith, supra, at Ex. E, Tab 53).)

Additionally, during cross-examination Dr. Staats acknowledged that anaphylaxis can

produce systemic inflammation within less than an hour of vaccination. (Id. at 150-51.)

However, on further questioning from the undersigned, Dr. Staats explained that

cytokines are a category of molecule that encompasses many different proteins.

Whereas Dr. Kinsbourne’s theory relies on a specific cytokine in IL-1β, “vaccines may

induce an array of proinflammatory cytokines” and “those proinflammatory cytokines

may be something other than IL-1.” (Id. at 153.) Dr. Staats explained that he has cited

papers that show, “where it has been measured, IL-1 was not one of the cytokines that

came up early.” (Id. at 154-55 (discussing Valensi, Carlson, & Van Nest, supra, at Ex.

E, Tab 1; Buglione-Corbett, supra, at Ex. E, Tab 43; Nakayama et al., supra, at Ex. E,

Tab 44).)

In contrast, when asked directly if the onset in this case was “too soon after her

vaccination” to infer causation, Dr. Kinsbourne indicated, “

We have no way of rationalizing that. We don’t know. . . . [T]here’s nothing

to tell us that it’s going to happen after, say, two hours, after one hour. . . .

[H]ow many hours something takes really we don’t have knowledge of

mechanism that exquisite. . . . I think it’s perfectly possible as far as we

know.

(Id. at 48.) This answer offers no attempt to meaningfully grapple with the timing issue

and, even accounting for the limitations of the cited literature, Dr. Staats’ competing

testimony refutes this assertion that the issue cannot be rationalized or meaningfully

explored based on the mechanism Dr. Kinsbourne himself proposed. Dr. Staats not

only establishes that there is a body of literature touching on this issue, but that

familiarly with that literature actually suggests reasons to conclude that the timing relied

upon by Dr. Kinsbourne is suspect. During cross examination, Dr. Kinsbourne had a

further exchange with respondent’s counsel illuminating on this point:

Q: And let’s talk about the minimum time frame. You wrote in your first

report and you testified here today that there’s not really a minimal

temporal interval stipulated based on the medical literature. Is that

correct?

A: I haven’t seen anybody say it can’t happen sooner than X.

Q: And even as someone without experience in research in cytokines, we

can agree that it takes time for the body to create proinflammatory

cytokines in response to vaccination and that it would take time for them to

[reach] the brain. Correct?

A: Yes.

40

Q: So, for example, if someone has a seizure 30 seconds after

vaccination, that’s not likely to be due to proinflammatory cytokines

created in response to the vaccine. Is that correct?

A: Well, it sounds correct. I haven’t really thought about it, of course, but

see, what – as I stated, if the seizure threshold is low, it can be tipped over

very fast. Now, how fast, very fast is, I really can’t say. But I don’t see –

I’m not aware of evidence that rules out one hour as being a sufficient

interval. It’s not something we can guess at.

(Id. at 66-67.)

Importantly, petitioner bears the burden of proof under Althen prong three and

Dr. Kinsbourne’s testimony effectively confirms she cannot meet that burden. The

Federal Circuit has cautioned against setting “hard and fast” deadlines for onset. Paluck

v. Sec’y of Health & Human Servs., 786 F.3d 1373, 1383-84 (Fed. Cir. 2015). However,

the Court of Federal Claims has also previously observed that while the Althen Court

rejected the need for scientific certainty, “in ‘a field bereft of complete and direct proof of

how vaccines affect the human body,’ . . . . [t]he standard of proof does not operate as a

sliding scale that varies depending upon the quantity and quality of the scientific

evidence that is available.” Caves v. Sec’y of Health & Human Servs., 100 Fed. Cl.

119, 143 (2011) (quoting Althen, 418 F.3d at 1280), aff’d, 463 F. App’x 932 (Fed. Cir.

2012). Here, the fact that Dr. Kinsbourne cannot locate medical literature disproving his

opinion does not render it supported, especially where Dr. Kinsbourne’s own testimony

suggests he has not even thought the issue through himself.

On the whole, while Dr. Kinsbourne has disclaimed any need or ability to

determine whether his own theory could unfold over the course of as little as one hour,

Dr. Staats has provided a far more detailed presentation persuasively opining that it is

less likely that it could, given the mechanisms actually underlying Dr. Kinsbourne’s

proposed theory. Accordingly, there is not preponderant evidence that it is medically

reasonable to infer causation in this case based on Dr. Kinsbourne’s proffered theory.

Thus, I find that petitioner has not satisfied Althen prong three.

f. Weighing the Expert Testimony

Where both parties offer expert testimony, a special master's decision may be

“based on the credibility of the experts and the relative persuasiveness of their

competing theories.” Broekelschen v. Sec'y of Health & Human Servs., 618 F.3d 1339,

1347 (Fed. Cir. 2010) (citing Lampe, 219 F.3d at 1362). Nothing requires the

acceptance of an expert's conclusion “connected to existing data only by the ipse dixit of

the expert,” especially if “there is simply too great an analytical gap between the data

and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner,

522 U.S. 136, 146, 118 S. Ct. 512, 139 L.Ed.2d 508 (1997)); see also Isaac v. Sec'y of

Health & Human Servs., No. 08–601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr.

July 30, 2012), mot. for review den'd, 108 Fed. Cl. 743 (2013), aff'd, 540 Fed. Appx. 999

41

(Fed. Cir. 2013) (citing Cedillo, 617 F.3d at 1339). Weighing the relative persuasiveness

of competing expert testimony, based on a particular expert's credibility, is part of the

overall reliability analysis to which special masters must subject expert testimony in

Vaccine Program cases. Moberly, 592 F.3d at 1325–26 (“[a]ssessments as to the

reliability of expert testimony often turn on credibility determinations”); see also Porter v.

Sec'y of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this court has

unambiguously explained that special masters are expected to consider the credibility of

expert witnesses in evaluating petitions for compensation under the Vaccine Act”).

Respondent asserts in his briefing that Dr. Kinsbourne’s credentials do not

include any specialized education, training, or expertise in pediatric immunology or

seizure disorders and that he has no prior experience studying, or working with,

cytokines or immune responses to vaccination and the potential effect on seizure

threshold in children. (ECF No. 79, p. 13-15.) Respondent argues that, apart from his

one year of pediatric residency in 1958-1959 and board certification in 1968, Dr.

Kinsbourne’s pediatric experience is limited to neuropsychology. (Id. at 13.)

Respondent further stresses that the length of time since Dr. Kinsbourne has clinically

treated a patient creates doubt about his qualification to opine on the medical issues in

this case. (Id. at 14.) Due to lack of experience in pediatric immunology and seizure

disorders, respondent submits that I should apply less weight to Dr. Kinsbourne’s

opinions when compared to Dr. Holmes, who is a practicing clinical pediatric neurologist

with special interest in seizure disorders and epilepsy. (Id.)

Respondent’s point is well taken. See Bangerter ex rel. D.B., 2022 WL 439535,

at *30. But see Eilan ex rel. A.E. v. Sec’y of Health & Human Servs., No. 15-381V, 2021

WL 1085925, at *29-31 (Fed. Cl. Spec. Mstr. Feb. 23, 2021). Both Drs. Kinsbourne and

Holmes have the requisite training in neurology to be accepted as experts. However,

Dr. Holmes’ clinical and research experience is more up-to-date and more relevant to

the issues addressed. Dr. Holmes currently holds a position as Physician Leader in

Neurology Health Care Service at Fletcher Allen Health Care in Burlington, Vermont, as

well as positions as Professor and Chair of Neurological Sciences and Professor of

Pediatrics at the University of Vermont College of Medicine. (Ex. B, p. 2.) Before that,

his work focused specifically on childhood epilepsy, including, for instance, his role as

Director of Pediatric Epilepsy Program at Talmadge Hospital in Augusta, Georgia, as

well as his roles as Director of Clinical Neurophysiology Laboratory and Epilepsy

Program and Director of the Center for Research in Pediatric Epilepsy at Children’s

Hospital in Boston, Massachusetts. (See id.) He has been on the editorial boards of

several scientific journals focused on epilepsy and participated in countless lectures on

the subject of epilepsy. (See id. at 6-7, 15-33.) He also written hundreds of peer-

reviewed articles, abstracts, chapters, and books on the topic of epilepsy. (Tr. 82.)

On the other hand, Dr. Kinsbourne has not maintained a clinical practices since

the early 1990s. (Tr. 56; Ex. 8, p. 2.) While he submits that he has continued to keep

up with the field (Tr. 29), Dr. Holmes indicated that a clinical practice is essential to

staying up-to-date in such an evolving field. (Id. at 80). Moreover, in his current

positions, Dr. Kinsbourne teaches graduate students, not medical students, and he

could not say for certain whether he has published, researched, or taught about seizure

42

disorders in the past 30 or so years. (Id. at 29, 56.) As for respondent’s contention that

Dr. Kinsbourne lacks sufficient experience in pediatric neurology, Dr. Kinsbourne held

significant professorships in pediatric neurology toward the beginning of his career and

testified to his specific training in pediatric neurology, albeit many decades ago. (Id. at

28-29; Ex. 8, p. 1-2.) Even so, a comparison of their respective curricula vitae reveals

that Dr. Holmes has more clinical and research experience in childhood epilepsy

specifically. While Dr. Kinsbourne was proffered to testify as an expert without

objection, the length of time he has been out of active clinical practice and the

differences between his and Dr. Holmes’s experience are too extreme to go

unmentioned. Dr. Holmes’ opinion is clearly entitled to comparatively more weight.32

Additionally, in determining whether a particular expert's testimony was reliable

or credible, a special master may consider whether the expert is offering an opinion that

exceeds the expert's training or competence. Walton v. Sec'y of Health & Human

Servs., No. 04–503V, 2007 WL 1467307, at *17–18 (Fed. Cl. Spec. Mstr. Apr. 30, 2007)

(otolaryngologist not well suited to testify about disciplines other than her own

specialty). While all testimony of the experts offered at the entitlement hearing was

heard and considered, a special master may properly evaluate, and give appropriate

weight to, whether certain testimony is beyond a particular expert's purview. See, e.g.,

King v. Sec'y of Health & Human Servs., No. 03-584V, 2010 WL 892296, at *78–79

(Fed. Cl. Spec. Mstr. Mar. 12, 2010) (petitioner's expert far less qualified to offer opinion

on general causation issues pertaining to autism than specific issues pertaining to the

petitioner's actual medical history, given the nature of the expert's qualifications).

It is also concerning that Dr. Kinsbourne’s theory relating to cytokines relies so

heavily on immunology when his opinion differs so much from respondent’s expert, Dr.

Staats, who has far more relevant expertise in immunology. (See, e.g., Ex. 7, p. 3.)

While neurologists must have some latitude to discuss immunologic causes of

neurologic injuries, Dr. Kinsbourne is not an immunologist or a neuro-immunologist.

Although Dr. Kinsbourne testified to the overlap between neurology and immunology

(Tr. 55), he acknowledged having no professional training with respect to cytokines (id.),

reducing his credibility on the very subject that forms the core of his theory. Accord

Bangerter ex rel. D.B., 2022 WL 439535, at *30 (recognizing that a special master’s

32

Martin v. Sec’y of Health & Human Servs., No. 15-789V, 2020 WL 4197748, at *7, 31 (Fed. Cl. Spec.

Mstr. May 8, 2020), aff’d, Martin v. Sec’y of Health & Human Servs., No. 15-789V, slip op (Fed. Cl. 2020)

(“Dr. Kinsbourne . . . has no demonstrated research or treatment expertise in the matters in dispute, and

he relies on neurology expertise that has not been honed or refined, whether by clinical practice or

research, for nearly 30 years.”); Jaafar v. Sec’y of Health & Human Servs., No. 15-267V, 2018 WL

4519066, at *3 (Fed. Cl. Spec. Mstr. Aug. 10, 2018) (concluding that petitioner did not establish DTaP

vaccination caused infantile spasms and noting that “the most recent phase of [Dr. Kinsbourne’s] career

has had a shallower connection to pediatric neurology clinical care.”); Holmes, 2011 WL 2600612 at *20

(questioning Dr. Kinsbourne’s “clinical expertise in diagnosing and treating febrile seizures and epilepsy”);

Stone v. Sec’y of Health & Human Servs., No. 04-1041V, 2010 WL 1848220, at *8 (Fed. Cl. Spec. Mstr.

Apr. 15, 2010), review granted, judgment rev’d sub nom; Stone v. Sec’y of Health & Human Servs., 95

Fed. Cl. 233 (2010) (“The fact that for the past twenty-five years Dr. Kinsbourne has not focused his

practice, research or teachings in the field of seizure disorders, . . . significantly limited his ability to offer

reliable, persuasive, and cogent testimony in this case.”); Hoskins v. Sec’y of Health & Human Servs., No.

15-071V, 2017 WL 3379270, at *5 (Fed. Cl. Spec. Mstr. July 12, 2017).

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determination of an expert reliability may depend on “whether the expert is offering an

opinion that exceeds the expert’s training or competence”). I have in the past been

critical of Dr. Kinsbourne for submitting expert opinions “beyond his areas of expertise

and into the field of immunology.” Id. Here, the difference in credentials between Dr.

Staats and Dr. Kinsbourne is particularly germane to the above analysis under Althen

prong three, where Dr. Kinsbourne effectively sought to equate the limitations of his own

personal knowledge with the limits of the relevant science.

VI. Conclusion

There can be no doubt that what S.H. and her family experienced during her

initial seizures and resulting treatment with anticonvulsants was frightening and

stressful, and for that, they have my sympathy. However, for all of the reasons

discussed above, I cannot conclude that S.H.’s seizures were vaccine-caused as there

is not preponderant evidence that the subject vaccines could or did cause her condition.

Therefore, I must conclude that petitioner is not entitled to compensation, and this case

is DISMISSED.

IT IS SO ORDERED.

s/Daniel T. Horner

Daniel T. Horner

Special Master

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